( 


ANEMIA 


SOME   OF   THE   DISEASES 


OF   THE 


BLOOD-FORMING   ORGANS 


DUCTLESS  GLANDS 


BYROM   BRAMWELL,  M.D.,  F.R.C.P.Ed.,  F.R.S.Ed. 

PHYSICIAN   TO   THE   ROYAL   INFIRMARY,   EDINBURGH  ;    LECTURER   ON   THE   PRINCIPLES 

AND    PRACTICE    OF    MEDICINE    AND    ON    CLINICAL    MEDICINE    IN   THE    SCHOOL 

OF   THE   ROYAL   COLLEGES,    EDINBURGH;    ETC.,    ETC. 


PHILADELPHIA 

P.  BLAKISTON'S   SON    &    CO. 

1012  WALNUT  STREET 
I  899 


PREFACE. 


This  book,  which  is  essentially  based  upon  my  own  clinical 
and  pathological  experience,  represents  a  great  deal  of 
clinical  observation  and  hard  work.  The  abstraction  of 
the  cases  and  the  preparation  of  the  tables,  for  which  I 
am  personally  responsible,  has  taken  much  longer  than 
I  had  anticipated  and  has  delayed  the  publication  ;  a  con- 
siderable portion  of  the  text  has  been  in  type  for  more 
than  a  year. 

My  sincere  thanks  are  due  to  Professor  Robert  Muir  and 
to  Dr  Lovell  Gulland  for  much  valuable  information  and 
kindly  criticism  ;  also  to  my  successive  House-Physicians — 
Drs  W.  G.  Aitchison  Robertson,  John  J.  Douglas,  D. 
Chalmers  Watson,  J.  H.  Henderson,  Edwin  Bramwell, 
Horace  C.  Colman,  John  W.  Struthers,  and  George  W. 
Miller — for  valuable  assistance  in  the  observation  and 
recording  of  the  hospital  cases,  in  making  blood-counts,  &c. 


B.  B. 


23  Drumsheugh  Gardens, 

Edinburgh,  April  1899. 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/anmiasomeofdisOObram 


CONTENTS. 


Introduction    - 

Anaemia   - 

Chlorosis 

Pernicious  Anaemia     - 

Cases  of  Pernicious  Anaemia 

l.eucocyth./emia 

Hodgkin's  Disease 

Addison's  Disease 

Cases  of  Addison's  Disease  - 

Myxcedema 

Cases  of  Myxcedema  - 

Exophthalmic  Goitre 

Acromegaly 

Cases  of  Acromegaly 

Appendix  - 

Index 


PAGE 

I 


56 
IO9 

139 
176 

212 
267 
287 
338 
33l 
421 
436 

443 

445 


ANEMIA 


AND 


SOME   OF  THE   DISEASES 


OF   THE 


BLOOD-FORMING    ORGANS    AND 
DUCTLESS    GLANDS. 


Introduction. — The  diseases  of  the  blood,  blood-forming  organs 
and  ductless  glands,  are  of  great  interest  and  importance.  During 
the  past  decade  many  important  facts  have  been  ascertained 
regarding  the  functions  of  the  ductless  glands  ;  and  it  is  hardly- 
necessary  to  say  that  our  knowledge  of  the  diseases  of  these 
important  organs  is  much  more  complete  than  it  was  a  few  years 
ago.  I  desire  specially  to  emphasise  the  fact  that  this  advance  in 
our  physiological,  as  well  as  our  pathological  and  clinical,  knowledge 
is  largely  due  to  clinical  observation  and  research.  Further,  in  the 
case  of  one  of  the  affections  included  under  this  group  of  diseases — 
I  refer  to  myxcedema — we  are  now  not  only  intimately  acquainted 
with  the  pathology  and  clinical  history  of  the  disease,  but,  what  is 
much  more  important,  we  know  how  to  treat  it  and  how  to  cure  it. 

The  diseases  of  the  blood,  blood-forming  organs  and  ductless 
glands  which  I  propose  more  particularly  to  consider  in  this  work 
are : — Chlorosis,  Pernicious  Anaemia,  Leucocythaemia,  Hodgkin's 
Disease,  Addison's  Disease,  Myxcedema  and  Sporadic  Cretinism, 
Exophthalmic  Goitre  and   Acromegaly.     Some  of  these  diseases, 


2  DISEASES   OF   THE   BLOOD. 

such  as  chlorosis  and  exophthalmic  goitre,  are  common  ;  others, 
such  as  leucocythaemia,  Hodgkin's  disease,  Addison's  disease  and 
acromegaly,  are  rare.  The  relative  frequency  of  these  diseases 
in  14,777  consecutive  cases  which  have  come  under  my  notice 
is  respectively  as  follows  : — 


Chlorosis           - 

-       314 

Pernicious  Anaemia      - 

45 

Leucocythaemia            - 

5 

Hodgkin's  Disease       - 

12 

Addison's  Disease        - 

12 

Myxcedema  and  Sporadic  Cretinism   - 

40 

Exophthalmic  Goitre  - 

79 

Acromegaly     - 

3 

But  it  must  be  remembered  that  these  figures  do  not  represent 
the  actual  frequency  of  some  of  these  diseases.  The  number  of 
cases  of  pernicious  anaemia  and  myxcedema  is,  for  example,  much 
above  the  average  ;  this  is  due  to  the  fact  that  a  considerable 
proportion  of  the  cases  were  seen  in  consultation  practice. 


ANAEMIA. 

Definition. — Anaemia  may  be  defined  as  a  condition  in  which, 
•either,  (a)  the  blood  as  a  whole ;  or  (J?)  the  red  blood  corpuscles 
or  (t-)  the  haemoglobin,  in  particular,  are  diminished  in  amount. 

Some  writers  make  the  definition  still  wider,  but  that  given 
above  is,  I  think,  quite  sufficiently  comprehensive  for  all  practical 
>urposes. 

The  term  oligcejnia  is  sometimes  applied  to  those  cases  of 
inaemia  in  which  the  blood  is  deficient  as  a  whole,  i.e.,  in  which  all 
)f  its  constituents  are  diminished  en  bloc ;  the  term  oligocythemia 
/to  those  cases  in  which  the  defect  is  chiefly  a  reduction  of  the  red 
blood  corpuscles  ;  and  the  term  oligochromcemia  to  those  cases  in 
which  the  defect  is  chiefly  a  reduction  of  the  haemoglobin  or 
colouring  matter. 

Classification  and  Etiology. 

Strictly  speaking,  anaemia  or  bloodlessness  is,  in  the  great 
majority  of  cases,  a  symptom,  comparable  to  dropsy  or  jaundice, 
rather  than  a  disease.  It  may  result  from  many  different  morbid 
•conditions. 

(i.)  In  some  affections,  as  in  chlorosis  and  pernicious  anaemia, 
the  anaemia  or  bloodlessness  is  the  most  striking  clinical  and 
pathological  feature  of  the  case.  These  we  at  present  term  the 
primary  anaemias,  for  as  yet  our  information  as  to  their  exact  cause 
is  somewhat  indefinite  and  obscure. 

The  terms  essential  and  idiopathic  have  also  been  applied  to 
these  forms  of  anaemia ;  but  since  the  same  terms  {essential  and 
idiopathic)  have  been  by  many  writers  restricted  to  a  special  form 
of  primary  anaemia  (viz.,  pernicious  anaemia),  they  are  apt,  if  used 
as  synonyms  for  primary  anaemia  (all  the  forms  of  primary  anaemia), 
to  give  rise  to  confusion,  and  should,  therefore,  in  this  sense  be 
discontinued. 

Dr  Pye-Smith  has  suggested  that  the  term  cytogenetic  anaemia 
should  be  applied  to  those  forms  of  anaemia  in  which  the  bloodless- 


4  DISEASES   OF   THE   BLOOD. 

ness  is  due  to  functional  disturbance  or  organic  disease  of  the 
blood-forming  organs  (the  marrow  of  the  bones,  the  spleen,  and  the 
lymphatic  glands).  But  I  doubt  whether  in  the  present  position  of 
our  knowledge  it  is  advisable  to  classify  these  so-called  cytogenetic 
forms  of  anaemia  under  a  separate  heading.  They  are  in  reality 
primary  anaemias,  and,  if  separately  grouped  under  a  special  term 
(cytogenetic),  should  be  merely  regarded  as  a  sub-group  of  the 
primary  anaemias. 

(2.)  In  other  cases  of  anaemia,  the  bloodlessness  is  obviously 
secondary — the  result  of  such  conditions  as: — (a)  loss  of  blood; 
(b)  the  presence  of  a  poison  introduced  into  the  blood  from  without; 
{c)  defective  nutrition  ;  or  {a)  well-defined  disease  in  some  of  the 
tissues  and  organs  of  the  body,  other  than  the  blood-forming  organs 
strictly  so-called,  such  for  example  as  cancer  of  the  stomach. 
These  we  term  the  secondary  or  symptomatic  anaemias. 

This  classification  is  clinical  and  practical  rather  than  strictly 
pathological  and  scientific.  It  is  probable  that  as  our  etiological 
and  pathological  knowledge  advances  some  of  the  cases  of  anaemia 
which  we  at  present  consider  primary — I  refer  more  particularly  to 
some  cases  of  pernicious  anaemia — will  be  found  to  be  secondary. 

Further,  it  must  be  remembered  that  in  the  present  position  of 
our  knowledge  it  is  not  always  possible  to  differentiate  during 
life  (clinically)  the  different  sub-varieties  of  primary  anaemia,  nor 
even  (in  some  cases)  to  say  with  absolute  certainty  whether  the 
anaemia  is  primary  or  secondary.  There  seems,  for  example,  some 
reason  to  suppose  that  in  rare  cases  the  clinical  condition  to  which 
the  term  pernicious  anaemia  is  applied  may  be  due  to  a  primary 
disease  of  the  marrow  of  the  bones ;  in  other  words,  in  some  cases 
this  form  of  primary  anaemia,  i.e.,  progressive  pernicious  anaemia 
(which,  as  I  will  afterwards  point  out,  is  usually  the  result  of 
excessive  blood  destruction  and  not  of  imperfect  blood  formation), 
is  perhaps  the  result  of  imperfect  blood  formation.  Again,  there  is, 
I  think,  some  reason  to  suppose  that  an  anaemia,  which  is  at  first 
merely  secondary  and  symptomatic,  may,  if  sufficiently  severe  and 
sufficiently  prolonged,  ultimately  assume  all  the  clinical  features  of 
the  pernicious  form.  But  I  need  not  enter  into  details  regarding 
these  very  difficult  and  debatable  questions.  I  will  refer  to  them 
again  when  I  come  to  consider  the  pathology  of  pernicious  anaemia 
in  more  detail. 

From  what  I  have  just  stated  it  will  be  obvious  that  in  the 
present  position  of  our  knowledge  it  is  convenient  to  divide  cases 
of  anaemia  into  two  great  groups,  viz.,  primary  and  secondary;  but 
as  soon   as  we  have  more  accurate  information  as  to  the  exact 


ANAEMIA.  5 

causation  and  pathology  of  the  different  forms  of  primary  anaemia 
this  classification  will  no  doubt  be  discarded. 

A  scientific  classification  of  anaemia  should  in  my  opinion 
aim  at : — 

Firstly,  dividing  all  cases  of  anaemia  into  two  great  groups, 
viz. : — 

(i.)  Cases  of  anaemia  due  to  excessive  blood  destruction,  loss 

of  blood,  etc.  ;  and 
(2.)  Cases  of  anaemia  due  to  imperfect  blood  formation. 

And  secondly,  determining  the  exact  seat  and  cause  of  (a)  the 
excessive  blood  destruction,  blood  loss,  etc.,  and  (fr)  of  the  imperfect 
blood  formation,  respectively. 

In  some  cases  in  which  all  the  clinical  characteristics  of  anaemia 
are  present  and  in  which  the  red  blood  corpuscles  are  diminished 
in  number  and  the  haemoglobin  deficient,  the  white  corpuscles 
are  enormously  increased.  To  these  cases  the  term  leukemia  or 
leucocythemia  is  applied.  Leucocythaemia  includes,  as  we  shall 
presently  see,  at  least  two  varieties  which  are  perhaps  separate 
diseases,  viz.,  the  spleno-medullary  and  lymphatic  forms  of 
leucocythaemia. 

Further,  there  is  perhaps  reason  to  suppose  that  in  rare  cases 
leucocythaemia  may  result  from  a  diseased  condition  of  the  bone- 
marrow,  the  spleen  and  lymphatic  glands  being  unaffected,  or  from 
a  diseased  condition  of  the  spleen,  the  marrow  of  the  bones  and 
the  lymphatic  glands  being  unaffected. 

The  symptomatic  and  secondary  anaemias  need  not  detain  us. 
It  is  the  anaemias  included  under  the  first  group — the  primary 
anaemias  (under  which  I  include  the  so-called  cytogenetic  forms) — 
to  which  I  wish  particularly  to  refer. 

The  more  important  causes  of  anaemia. — But  before  con- 
sidering the  individual  forms  of  primary  anaemia,  it  may  perhaps 
be  well  to  enumerate  the  more  important  causes  of  anaemia  and  to 
classify  these  causes  in  certain  groups.     They  are  as  follows  : — ■ 

(a.)  Hemorrhage. — Sudden  and  profuse  haemorrhage  from  an 
external  wound  or  from  an  internal  ulceration  such  as  an  ulcer  of 
the  stomach,  and  the  prolonged  drain  of  large  or  small  quantities  of 
blood  which  may  result  from  haemorrhoids,  menorrhagia,  etc.,  only 
of  course  require  to  be  mentioned  as  causes  of  profound  anaemia. 

In  middle-aged  and  old  people,  profound  anaemia  is  not  unfre- 
quently  due  to  bleeding  piles.  I  have  also  seen  a  profound  condition 
of  anaemia,  which  presented  many  of  the  clinical  characteristics  of 
the  pernicious  form,  due  to  a  long-continued  drain  of  blood  from 
the  uterus. 


6  DISEASES   OF   THE   BLOOD. 

The  profound  anaemia  which  is  in  some  cases  associated  with 
the  presence  in  the  duodenum  of  the  ankylostoma  duodenale 
is  probably  in  great  part  due  to  loss  of  blood  ;  these  parasites 
attach  themselves  to  the  mucous  membrane  and  suck  the  blood 
from  the  minute  vessels.  In  aggravated  cases  of  this  kind,  the 
clinical  condition  closely  simulates,  and  in  some  cases  is  perhaps 
identical  with,  that  characteristic  of  pernicious  anaemia.  Dr  William 
Hunter  has  suggested  that  the  ankylostoma  duodenale  leads  to 
the  production  of  this  profound  form  of  anaemia,  not  so  much  by 
loss  of  blood  as  by  the  production  of  a  poisonous  substance  which,, 
being  absorbed  into  the  portal  circulation,  exerts  a  destructive 
influence  upon  the  red  blood  corpuscles.  I  shall  return  to  this 
point  when  I  come  to  describe  the  pathology  of  pernicious  anaemia 
in  more  detail. 

{b.)  Deficiency  of  food,  improper  food,  unhealthy  surroundings \ 
want  of  sunlight,  etc. 

(c.)  Functional  derangements  or  organic  disease  of  the  stomach  or 
intestine  which  interfere  with  the  digestion  and  absorption  of  food. — 
In  some  cases  of  cancer  of  the  stomach,  very  profound  anaemia  is 
developed.  In  these  cases  the  anaemia  is  doubtless  due  to  a 
variety  of  different  causes  acting  in  combination,  and  not  merely 
to  a  defect  in  the  digestion  and  absorption  of  food. 

Under  this  head  are  included  those  derangements  and  diseases  of 
the  gastro-intestinal  tract  which  prevent  the  absorption  of  iron  from 
the  food  into  the  blood  ;  this  is  perhaps  an  important  element  in 
the  causation  of  chlorosis  (one  of  the  primary  forms  of  anaemia). 

(d.)  The  presence  of  certain  parasites  and  poisonous  substances 
{chemical  and  organic)  in  the  blood  {the  malarial  parasite,  lead, 
arsenic,  mercury,  etc.). —  Under  this  head  it  is  convenient  to  include 
the  anaemia  which  develops  in  the  course  of  many  febrile  and 
infectious  diseases  (rheumatic  fever,  ulcerative  endocarditis,  typhoid, 
syphilis,  etc.),  though  in  such  conditions  the  anaemia  may  doubtless 
be  due  to  a  number  of  different  factors. 

Dr  Robert  Muir  has  suggested  to  me  that  malarial  ancemia 
should  be  placed  under  a  separate  heading,  since  the  mode  in 
which  the  malarial  parasite  destroys  the  red  corpuscles  is  now  so 
well  established. 

{e.)  Long-continued  diarrhoea,  prolonged  suppuration,  a  prolonged 
drain  of  albuminous  material  from  the  blood,  as  in  Bright 's  disease, 
leucorrJicea,  and  other  similar  conditions. — And  here  I  may  state 
that  one  of  the  most  profound  cases  of  anaemia  which  I  have  ever 
seen  was  due  to  long-continued  diarrhoea  in  a  case  of  sprue  ; 
possibly  this  was  not  merely  the  result  of  the  diarrhoea,  but  of  the 


AN/EMIA.  7 

absorption  into  the  blood  of  some  poison  (a  micro-organism  or  its 
toxin). 

(_/!)  Derangement  or  disease  of  the  blood-forming  organs  (bone- 
marroiv,  spleen  and  lymphatic  glands),  which  is  attended  with  the 
defective  production  and  formation  of  red  blood  corpiiscles. 

(g.)  Derangement  or  disease  of  the  blood-destroying  organs  {the 
gastro-intestinal  mucosa,  the  spleen,  the  liver,  and,  to  a  slight  extent, 
the  marrow  of  the  bones')  associated  zvith  an  increased  destruction  of 
red  blood  coipuscles. 

In  considering  the  different  forms  of  primary  anaemia  and  their 
differential  diagnosis,  I  shall  have  to  point  out  how  necessary  it  is, 
before  coming  to  the  conclusion  that  the  anaemia  is  primary,  to 
exclude  all  the  possible  causes  of  secondary  anaemia  which  have 
been  enumerated  in  the  foregoing  headings.  The  point  is  of  so 
much  importance  that  I  emphasise  it  here. 

The  conditions  which  are  included  in  the  foregoing  heads  may 
be  arranged  in  three  great  groups,  viz.  : — 

Group  i. — This  includes  those  cases  (a)  in  which  the  anaemia 
is  due  to  conditions  which  interfere  with  the  elaboration  of  the 
materials  which  are  essential  to  maintain  the  blood  in  a  condition 
of  health  ;  and  (b)  in  which  the  anaemia  is  due  to  defective  blood 
formation  (functional  derangement  or  organic  disease  of  the  blood- 
forming  organs  properly  so  called). 

Group  2. — This  includes  those  cases  in  which  the  anaemia  is  due 
(a)  to  direct  loss  of  blood,  or  to  a  prolonged  drain  of  the  albuminous 
materials  of  the  blood  from  the  system  ;  and  (J?)  to  excessive  blood 
destruction  (functional  derangement  or  organic  disease  of  the  blood- 
destroying  organs  or  poisons  in  the  blood). 

Group  3. — This  includes  those  cases  in  which  the  anaemia  is 
due  both  to  excessive  blood  destruction  and  to  defective  blood 
formation,  acting  in  combination. 

As  a  matter  of  fact,  in  many  cases  of  anaemia  the  bloodlessness 
is  due  to  a  number  of  different  causes  acting  in  association.  The 
profound  anaemia  which  is  present  in  some  cases  of  rickets,  for 
example,  may  be  partly  the  result  of  deficient  or  imperfect  feeding, 
partly  the  result  of  want  of  sunlight,  insanitary  surroundings, 
insufficient  clothing,  exposure  to  cold  and  damp,  and  partly  the 
result  of  disease  of  the  blood-forming  or  blood-destroying  organs 
(the  marrow  of  the  bones,  liver,  spleen,  etc.).  It  is  not  unreasonable, 
I  think,  to  suppose  that  in  many  cases  of  rickets  the  bone-marrow 
is  functionating  imperfectly  ;  further,  it  must  be  remembered  that  in 
aggravated  cases  of  rickets,  more  particularly  I  think  in  those  cases- 
in  which  congenital  syphilis  is  also  present,  the  liver  and  spleen  are 


8  DISEASES   OF   THE   BLOOD. 

enlarged  and  diseased.  I  may  take  this  opportunity  of  stating 
that  in  some  cases  of  this  kind  (rickets  with  enlargement  of  the 
liver  and  spleen)  the  microscopical  characters  of  the  blood  closely 
resemble  those  of  pernicious  anaemia  ;  and  further,  that  in  children 
it  is  sometimes  very  difficult,  from  the  mere  microscopical  char- 
acters of  the  blood,  to  draw  a  distinction  between  pernicious 
anaemia  and  pseudo-leucocythaemia. 

Again,  although  in  many  cases  of  pernicious  anaemia  the  primary 
change  appears  to  be  an  increased  destruction  of  the  red  blood 
corpuscles,  there  is  at  the  same  time  a  too  rapid  and  consequently 
defective  blood  formation. 

The  seats  of  blood  formation  and  destruction  in  health. — 
In  connection  with  some  of  the  foregoing  statements  it  may  be 
advisable  to  point  out  that  in  health,  the  composition  of  the  blood, 
the  number  of  red  blood  corpuscles  and  the  total  amount  of 
haemoglobin  are  maintained  at  a  tolerably  uniform  standard.  The 
destruction  of  red  corpuscles  which  is  constantly  going  on  is 
accurately  met  by  the  production  of  new  red  blood  corpuscles. 

The  average  duration  of  a  red  blood  corpuscle  appears  to  be 
about  two  weeks  or  less. 

In  health,  the  red  marrow  of  the  bones  is  the  chief,  and  probably 
the  only,  seat  of  the  production  of  the  red  corpuscles.  And  here  it 
may  be  well  to  state  that  the  nucleated  red  corpuscle,  which  is 
normally  present  in  the  marrow  of  the  bones,  is  the  antecedent  of 
the  ordinary  non-nucleated  red  corpuscle  which  is  found  in  the 
blood.  In  some  conditions  of  disease,  and  especially  when  the 
destruction  of  red  blood  corpuscles  is  excessive,  the  yellow  marrow 
of  the  long  bones  may  be  replaced  by  red  marrow — this  is  appa- 
rently a  compensatory  increase  of  the  blood-forming  tissue.  It 
would  appear  that  in  animals  (and  presumably  therefore  in  man) 
after  very  profuse  haemorrhage,  red  blood  corpuscles  may  be  pro- 
duced in  the  spleen.  Further,  it  has  been  suggested  that  occa- 
sionally, after  great  loss  of  blood,  or  excessive  blood  destruction, 
however  caused,  red  blood  corpuscles  may  also  be  produced,  but 
probably  only  in  a  very  limited  degree,  in  the  lymphatic  glands. 
Dr  Gulland,  however,  tells  me  that  this  view  is  probably 
erroneous. 

In  health,  the  chief  seats  of  the  destruction  of  the  red  blood 
corpuscles  appear  to  be  the  gastro-intestinal  mucosa  and  the  spleen. 
A  certain  amount  of  destruction  of  red  blood  corpuscles  also  seems 
to  take  place  in  the  bone- marrow. 

The  white  corpuscles  appear  to  be  chiefly  formed  in  the  lym- 
phatic   glands    partly  in   the   other   lymphoid    structures   (spleen, 


ANAEMIA.  9 

marrow    of  the    bones,    gastro-intestinal    lymph   follicles,    thymus 
gland,  and  tonsils). 

In  health,  the  haemoglobin  which  results  from  the  destruction  of 
red  blood  corpuscles  in  the  gastro-intestinal  mucosa  and  the  spleen 
is  carried  to  the  liver,  where  it  is  in  part  transformed  into  bile 
pigment  and  urinary  pigment.  It  would  appear  that  all  of  the  iron 
arising  from  the  disintegration  of  the  haemoglobin  is  not  excreted  ; 
a  considerable  portion  of  it  is  probably  retained  in  the  system  and 
re-utilised  in  blood  formation.  Stockman  concludes  as  the  result 
of  a  most  careful  analysis  of  the  iron  in  the  ordinary  dietaries  of 
healthy  people  with  ordinary  appetite  and  digestion  that  "  the 
iron-metabolism  of  the  body  must  be  very  small,  and  that  while 
the  pigment  of  disintegrated  red  blood  corpuscles  is  excreted,  in 
part  at  least,  as  the  colouring  matter  of  bile  and  urine,  their  iron  is 
carefully  retained  in  the  body  for  future  use."  * 

We  have  seen  that  in  some  cases  of  anaemia  the  bloodlessness 
is  the  chief  clinical  characteristic  of  the  case,  that  it  is  convenient 
to  term  the  anaemia  in  these  cases  primary ;  that  in  other  cases  the 
anaemia  is  secondary  and  symptomatic  ;  that  in  some  of  the  cases 
of  primary  anaemia  the  anaemia  is  due  to  disease  of  the  cytogenetic 
or  blood-forming  organs,  i.e.,  to  defective  blood  formation,  and  in 
others  to  increased  blood  destruction.  In  dealing  with  a  case  of 
anaemia  at  the  bedside,  it  is  of  the  utmost  importance  to  endeavour 
to  determine  in  which  of  these  groups  the  anaemia  should  be  placed  ; 
for  the  treatment  of  the  condition  largely  depends  upon  the  nature 
of  the  primary  cause,  whether,  for  example,  the  anaemia  is  due 
to  increased  destruction  or  defective  formation  of  the  red  blood 
corpuscles,  whether  it  is  the  result  of  a  deficiency  of  haemoglobin, 
etc.  But  I  repeat  that  it  is  not  always  easy  or  possible  to  come  to 
a  definite  conclusion  on  some  of  these  points.  It  is  sometimes, 
for  example,  extremely  difficult  to  differentiate  pernicious  anaemia 
from  profound  anaemia  associated  with  cancer  of  the  stomach,  the 
presence  of  parasites  in  the  intestine,  etc. 

Those  who  think  that  pernicious  anaemia  is  a  definite  and 
distinct  disease  say  that  in  these  cases  the  pernicious  anaemia  is 
superadded  to,  or  developed  upon,  the  original  (secondary)  form  of 
anaemia ;  others,  on  the  contrary,  suppose  that  the  condition  which 
we  term  pernicious  anaemia  may  be  the  result  of  a  number  of 
different  conditions  in  all  of  which  the  ultimate  blood  condition, 
clinically  speaking,  is  very  much  the  same.     It  seems  to  me  not 

*  "Journal  of  Physiology,"  Vol.  xxi.,  No.  i,  5th  February  1897. 


IO  DISEASES   OF   THE   BLOOD. 

improbable  that  an)-  profound  condition  of  anaemia  may,  provided 
that  it  is  sufficiently  severe  and  sufficiently  long  continued,  pass- 
into  the  pernicious  form — I  refer  more  especially  to  those  cases  in 
which  the  anaemia  is  the  result  of  loss  of  blood  and  increased  blood 
destruction.     But  I  will  discuss  this  question  more  in  detail  later. 

From  what  I  have  already  stated,  it  will  readily  be  understood 
that  a  general  description  of  the  different  varieties  of  anaemia 
which  are  included  under  these  groups  (whether  primary  or 
secondary)  is  insufficient ;  it  is  essential  to  consider  the  more 
important  forms  individually  and  in  detail.  But  before  doing  so  it 
will  certainly  be  convenient  and  advisable  to  give  a  brief  general 
description  of  the  clinical  symptoms  which  are  present,  in  a  more 
or  less  marked  degree,  in  all  cases  in  which  the  red  blood  corpuscles 
are  greatly  deficient  in  number  or  in  which  the  haemoglobin  is 
greatly  reduced  in  amount ;  and  to  refer  in  more  detail  than  I  have 
hitherto  done  to  the  etiology  and  pathology  of  anaemia,  using  the 
term  in  its  widest  and  most  general  sense. 

The  Clinical  Symptoms  associated  with  An.emia. 

The  chief  clinical  symptoms  and  signs  which  characterise  or  are 
associated  with  a  profound  degree  of  anaemia,  however  produced,. 
are  as  follows  : — 

Pallor  of  the  skin  and  mucous  membranes. — The  pallor  of  the 
mucous  membranes  (palpebral  conjunctiva,  inner  surface  of  the  lips, 
etc.)  is  much  more  important  as  a  sign  of  anaemia  than  the  colour 
of  the  skin  ;  for  in  some  cases  in  which  anaemia  is  very  marked,  the 
skin  is  not  pale  and  white.  In  many  cases  of  chlorosis,  for  example, 
the  skin  has  a  greenish  tint ;  in  pernicious  anaemia  it  is  usually 
of  a  lemon-yellow  tint,  occasionally  distinctly,  and  in  rare  cases 
markedly,  jaundiced  ;  in  Addison's  disease,  in  which  there  may  be 
some,  though  there  is  not  generally  any  marked  degree  of,  anaemia, 
the  skin  is  brown,  in  rare  cases  almost  black,  while  the  ocular  con- 
junctiva is  very  pale  and  glistening  ;  in  tertiary  syphilis,  in  which 
a  certain  amount  of  anaemia  is  usually  present,  the  skin  often  has 
a  ding)-  muddy  hue  ;  in  cancer,  more  particularly  cancer  of  the 
stomach  in  which  the  anaemia  is  often  very  marked,  the  skin  may 
have  a  yellow  cachectic  appearance.  On  the  other  hand  it  must 
be  remembered  that,  in  many  cases  in  which  the  skin  is  pale,  the 
lips  and  conjunctivae  are  well  coloured  and  there  is  no  anaemia. 

I  repeat  that  the  colour  of  the  mucous  membranes  is  more 
important  than  the  colour  of  the  skin  as  a  diagnostic  sign  of 
anaemia.     With  very  rare  exceptions,  the  mucous  membranes  are,. 


AN. -EM  I  A.  I  I 

in  well  -  marked  cases  of  anaemia,  markedly  pale  and  bloodless- 
looking.  But  in  exceptional  cases  this  is  not  so  ;  in  rare  cases  of 
splenic  leucocythaemia,  for  example,  the  lips  are  blue  and  the  face 
red  and  turgid.  To  this  condition  the  term  leukaemic  plethora  has 
been  given.  Further  information  is  required  as  to  the  number  of 
red  blood  corpuscles  which  are  present  in  cases  of  this  kind,  i.e.,  as 
to  the  degree  of  the  anaemia.  I  may  also  state  that  in  the  rare  condi- 
tion which  is  termed  diffuse  melanosis,  with  which  a  certain  degree 
of  anaemia  is  sometimes  associated,  the  mucous  membranes,  instead 
of  being  pale,  may  be  of  a  leaden  hue. 

The  degree  of  pallor  is  very  variable.  The  colour  of  the  mucous 
membranes  seems  to  depend  quite  as  much  (perhaps  more)  upon 
the  total  amount  of  haemoglobin  which  the  blood  contains  as  upon 
the  number  of  red  blood  corpuscles.  In  some  cases  of  chlorosis,  for 
example,  in  which  the  red  blood  corpuscles  are  only  slightly 
diminished  in  number,  but  in  which  the  haemoglobin  is  very  defi- 
cient, the  mucous  surfaces  of  the  lips  may  be  almost  absolutely 
bloodless-looking. 

Languor,  debility,  incapability  of  sustained  exertion  either  of  body 
or  mind. — These  are  prominent  symptoms  in  cases  of  profound 
anaemia. 

Shortness  of  breath  on  exertion  and  palpitation. — These  are  very 
characteristic  symptoms,  and  are  prominent  both  in  those  cases  of 
anaemia  in  which  the  red  blood  corpuscles  are  greatly  reduced  in 
number  and  in  those  cases  in  which  the  red  corpuscles  are  only 
slightly  reduced,  but  in  which  the  haemoglobin  is  markedly  defi- 
cient. In  well-marked  cases  of  chlorosis,  for  example,  shortness  of 
breath  on  exertion  and  palpitation  are  always  complained  of.  The 
shortness  of  breath  on  exertion  is  partly  due  to  the  deficiency  in 
haemoglobin,  partly  to  the  altered  condition  of  the  heart.  In  all  cases 
of  profound  anaemia,  if  long  continued,  the  heart  muscle  is  apt  to 
become  fatty,  and  is  in  a  condition  of  irritable  weakness.  Under 
such  circumstances,  palpitation  and  increased  frequency  of  the  heart 
and  pulse  are  easily  excited  by  comparatively  trifling  causes,  such 
as  slight  efforts,  mental  excitement,  etc. 

GEdema  of  the  feet. — In  profound  conditions  of  anaemia,  a  certain 
degree  of  oedema  of  the  feet  is  very  common.  It  is  no  doubt  in 
many  cases  partly  the  result  of  the  watery  condition  of  the  blood, 
but  is  chiefly  due  to  the  enfeebled  condition  of  the  heart.  CEdema 
of  the  feet  is  particularly  apt  to  arise  in  the  later  stages  of  anaemia 
and  in  those  cases  in  which  the  vasomotor  nerve  tone  is  enfeebled. 

Giddiness,  fainting,  headache,  etc. — In  well-marked  cases  of 
anaemia,  giddiness  is  usually  experienced  when  the  patient  stoops 


12  DISEASES   OF   THE   BLOOD. 

the  head  or  suddenly  rises  from  the  recumbent  to  the  erect  posi- 
tion ;  and  fainting  may  occur  as  the  result  of  comparatively  slight 
causes,  such  as  a  copious  watery  evacuation  of  the  bowels.  These 
symptoms  are  of  course  due  to  the  defective  supply  of  arterial 
blood  to  the  brain.  Headache,  noises  in  the  ear  (tinnitus),  a 
painful  feeling  of  throbbing  in  the  head,  are  also  in  many  cases 
complained  of. 

Irritability  of  temper,  peevishness,  and  diminished  emotional  con- 
trol are  common.  Neuralgia,  which  has  been  described  as  a  prayer 
on  the  part  of  the  nerves  for  a  better  supply  of  blood,  is  of  frequent 
occurrence.  In  the  advanced  stages  of  profound  anaemia,  especially 
in  the  pernicious  form,  an  extremely  painful  form  of  restlessness, 
which  is  no  doubt  due  to  the  want  of  oxygen  and  the  anaemic 
condition  of  the  nerve  centres,  is  often  developed  ;  and  delirium, 
a  semi-comatose  condition,  epileptiform  convulsions  and  coma  may 
occur. 

Loss  of  appetite,  dyspeptic  symptoms,  and  constipation. — These  are 
common  symptoms.  In  some  cases,  the  dyspepsia  and  anaemia  are 
due  to  a  common  cause,  as,  for  example,  cancer  of  the  stomach  ;  in 
others,  the  dyspeptic  symptoms  are  the  result  of  the  anaemia — the 
functional  and  structural  alterations  which  the  anaemic  condition 
produces  in  the  tissues  of  the  stomach. 

Constipation  is  a  prominent  symptom  in  many  cases  of  anaemia, 
especially  in  chlorosis  ;  indeed  the  late  Sir  Andrew  Clark  sup- 
posed that  chlorosis  is  due  to  constipation  and  the  resulting 
absorption  into  the  blood  of  excrementitious  products  produced  in 
the  intestine. 

In  other  cases  of  anaemia  there  is  diarrhoea.  It  is  rarely  the 
result  of  the  anaemia.  In  some  cases  it  appears  to  be  the  cause  of 
the  anaemia  ;  in  others,  it  is  an  associated  symptom — due  to  the 
functional  or  structural  alterations,  such  as  ulceration  in  the  gastro- 
intestinal tract,  with  which  the  anaemia  is  associated. 

In  chlorosis,  simple  perforating  ulcer  of  the  stomach  is  of 
frequent  occurrence  ;  and  in  such  cases,  it  is  often  a  difficult  matter 
to  determine  how  far  the  anaemia  is  due  to  the  chlorosis  or  how 
far  to  the  haematemesis  to  which  the  ulcer  of  the  stomach  may 
give  rise. 

Hemorrhages. — In  profound  conditions  of  anaemia,  bleeding 
from  the  mucous  surfaces  and  extravasations  of  blood  into  the 
internal  organs  are  apt  to  occur.  Epistaxis,  bleeding  from  the 
throat  and  bleeding  from  the  gums  are  especially  common.  Bleed- 
ing from  the  uterus  is  met  with  in  some  cases.  Hcematemesis  is  of 
frequent  occurrence  in  those  cases  of  chlorosis  in  which  the  stomach 


AN/EMIA.  13 

is  ulcerated,  but  is  comparatively  rare  in  other  forms  of  anaemia. 
Bleeding  from  the  bowel  occasionally  occurs.  Petechial  extravasa- 
tions in  the  skin  and  subcutaneous  tissue  are  occasionally  observed, 
and  minute  extravasations  of  blood  into  the  internal  tissues  {pleura, 
pericardium,  etc.),  are  frequently  found  after  death.  In  pernicious 
anaemia,  retinal  hemorrhages  are  very  common,  and  of  great  diag- 
nostic importance  ;  they  are  apt  to  occur  in  all  conditions  in  which 
the  red  blood  corpuscles  are  very  markedly  diminished  in  number ; 
they  are,  too,  frequently  met  with  in  leucocythaemia.  In  chlorosis, 
on  the  contrary,  in  which  the  defect  is  chiefly  a  diminution  of  the 
haemoglobin,  petechial  and  other  haemorrhages  (with  the  exception 
of  hsematemesis,  which  is  not  the  direct  result  of  the  anaemia  but 
due  to  associated  ulceration  of  the  stomach)  are  uncommon. 

The  general  state  of  nutrition. — In  many  cases  of  profound 
anaemia,  the  body  fat  is  well  preserved,  though  the  muscles  are 
usually  soft  and  flabby.  As  I  have  already  pointed  out,  a  con- 
tinued deficiency  of  haemoglobin  leads  to  the  production  of  a  fatty 
condition  of  the  internal  organs,  especially  of  the  heart,  and  is 
favourable  rather  than  otherwise  to  the  deposit  of  subcutaneous  fat. 
Marked  emaciation,  when  associated  with  profound  anaemia,  is 
strongly  suggestive  of  the  presence  of  some  associated  disease, 
such  as  cancer  of  the  stomach  ;  in  other  words,  is  suggestive  that 
the  anaemia  is  secondary  and  not  primary.  Nevertheless,  it  must 
be  remembered  that  in  some  cases  of  pernicious  anaemia  there  is 
considerable  loss  of  weight  and  in  rare  cases  decided  emaciation  ; 
this,  in  my  experience,  is  especially  apt  to  occur  in  those  cases  of 
pernicious  anaemia  in  which  there  is  long-continued  diarrhoea. 

Fever. — In  profound  conditions  of  anaemia,  intercurrent  febrile 
attacks  occasionally  occur.  They  are  especially  frequent  in  per- 
nicious anaemia.  The  pyrexia  is  in  some  cases  continuous,  in 
others  intermittent  or  remittent.  In  some  cases,  the  fever  seems 
to  be  the  direct  result  of  the  anaemic  condition,  or  perhaps  of  a 
poison  in  the  blood  which  is  the  cause  of  the  anaemia.  To  this 
form  of  fever,  the  terms  ancemic  fever  or  the  essential  fever 
of  anemia  have  been  applied.  In  other  cases,  the  fever  is  the 
result  of  associated  lesions  or  complications ;  in  others,  to 
the  unstable  condition  of  the  nerve  centres.  In  chlorosis,  true 
anaemic  fever  is  probably  very  rare.  When  pyrexia  occurs  in 
chlorosis,  the  elevation  of  temperature  is  usually  due  to  over-exer- 
tion, excitement,  etc.,  to  the  development  of  some  associated  lesion 
such  as  venous  thrombosis,  etc.,  or  to  some  independent  condition. 

The  condition  of  the  heart  and  vessels. — In  all  profound  condi- 
tions of  anaemia,  if  long  continued,  the  heart  muscle  is  apt  to  become 


14  DISEASES   OF   THE   BLOOD. 

fatty,  irritable  and  easily  excited,  and  the  heart  cavities  are  apt  to 
become  dilated.  Palpitation,  shortness  of  breath  on  exertion  and 
sudden  variations  in  the  frequency  of  the  pulse  are,  as  we  have 
seen,  prominent  symptoms  in  anaemia,  and  are  partly  due  to  this 
fatty  and  dilated  condition  of  the  heart  and  partly  to  the  incom- 
petence of  the  mitral  and  tricuspid  valvular  orifices  which  is  apt 
to  be  superadded. 

The  altered  condition  of  the  heart  is  in  some  cases  less  evident  on 
physical  examination  than  one  would  expect,  for  the  lungs  are  in 
many  cases — and  this  is  in  my  experience  especially  frequent  in  cases 
of  pernicious  anaemia — voluminous  and  hyper-resonant,  the  condition 
being  due  to  a  diffuse  emphysema.  The  apex  beat  may  be  displaced 
more  or  less  outwards  and  to  the  left.  The  cardiac  impulse  is  in 
many  cases  more  diffused  than  normal ;  during  any  temporary  excite- 
ment it  may  be  forcible,  at  other  times  it  is  usually  feeble.  The 
cardiac  dulness  both  to  the  right  and  to  the  left  is  usually  in- 
creased. Systolic  murmurs  may  be  audible  in  all  the  areas.  A 
pulmonary  systolic  murmur  is  by  far  the  most  frequent ;  but  I  shall 
refer  to  this  point  in  more  detail  when  I  come  to  describe  the  con- 
dition of  the  heart  in  chlorosis.  A  venous  hum  is  usually  present  in 
the  neck.  In  many  cases  of  profound  anaemia,  the  jugular  veins  are 
more  prominent  than  normal.  Pulsation  in  the  jugular  veins,  often 
slight  and  flickering,  but  in  some  cases  very  definite  and  marked  (and 
doubtless  due  to  tricuspid  incompetence),  may  also  be  developed. 

Profound  anaemia  if  long  continued — but  this  statement  applies 
more  especially  to  those  cases  in  which  the  red  blood  corpuscles  are 
markedly  diminished  in  number  (progressive  pernicious  anaemia, 
for  example),  rather  than  to  those  cases  in  which  the  haemoglobin 
is  merely  diminished  in  amount  (chlorosis) — is  apt  to  produce 
structural  (fatty)  changes  in  the  walls  of  the  minute  blood  vessels. 
This  is  in  all  probability  the  cause  of  the  haemorrhages,  more 
particularly  of  the  petechial  haemorrhages  (retinal  haemorrhages, 
for  example),  which  are  under  such  circumstances  of  frequent 
occurrence. 

The  condition  of  the  urine. — In  pernicious  anaemia  more  espe- 
cially, this  is  of  pathological  interest  and  of  some  diagnostic  value. 
In  most  cases  of  anaemia,  notably  in  chlorosis,  the  urine  is  paler 
than  normal  ;  in  other  cases — and  this  statement  more  particularly 
applies  to  cases  of  pernicious  anaemia,  especially  during  the 
intercurrent  attacks  of  blood  destruction  which  are  apt  to  be 
attended  with  fever  and  the  development  of  slight  jaundice — it  may 
be  more  highly  coloured  than  natural,  the  dark  colour  being  partly 
due  to  an  excess  of  pathological  urobilin. 


AN/EM  I  A.  15 

The  condition  of  the  blood  in  anaemia. — This  is  of  great 
importance.  The  characters  of  the  blood,  as  regards  the  number  of 
red  and  white  corpuscles,  the  total  amount  of  haemoglobin,  the 
richness  of  the  individual  corpuscles  in  haemoglobin,  and  the  micro- 
scopic appearance  which  the  formed  elements  of  the  blood  present, 
vary  considerably  in  different  forms  of  anaemia  and  in  the  same 
form  of  anaemia  in  accordance  with  the  severity  of  the  case.  Further, 
there  can  be  little  doubt  that  the  specific  gravity  of  the  blood  and 
the  nature  and  richness  of  the  soluble  constituents  of  the  plasma 
are  subject  to  great  variations  ;  but  our  knowledge  of  these  altera- 
tions is  as  yet  somewhat  indefinite. 

And  here  it  may  perhaps  be  well  to  say  a  few  words  with  regard 
to— 

The  clinical  examination  of  the  blood. — In  the  clinical  examination 
of  the  blood  in  anaemia,  the  chief  points  which  should  be  observed 
are  : — 

1.  The  naked-eye  characters  of  a  drop  of  blood  obtained  by 
puncturing  the  ear,  finger,  etc. 

2.  The  presence  or  absence  of  rouleaux  formation. 

3.  The  number  of  red  corpuscles. 

4.  The  total  amount  of  haemoglobin. 

5.  The  haemoglobin  richness  of  the  individual  red  corpuscles. 

6.  The  size,  shape,  and  microscopic  characters  of  the  red  blood 
globules. 

7.  The  number,  size,  shape,  and  microscopic  characters  of  the 
white  corpuscles,  and  the  way  in  which  they  react  to  staining 
reagents. 

8.  The  number  and  microscopic  characters  of  the  blood  plate- 
lets (including  Max  Schultze's  granular  masses,  which  seem  to  be 
masses  of  blood  platelets). 

9.  The  presence  of  other  formed  elements,  such  as  micro- 
organisms, pigment  granules,  crystals,  etc. 

10.  The  rapidity  with  which  the  fibrin  filaments  are  formed  and 
the  density  of  the  fibrin  network  in  a  drop  of  blood  examined 
under  the  microscope. 

11.  The  specific  gravity  of  the  blood. 

12.  The  "  reaction  "  of  the  blood. 

In  this  preliminary  sketch  of  the  condition  of  the  blood  in 
anaemia,  I  shall  not  attempt  to  describe  in  detail  the  minute  altera- 
tions which  are  characteristic  of  the  different  forms  of  anaemia,  but 
it  may  perhaps  be  well  to  direct  attention  to  some  of  the  more 
important  points. 

The  number  of  red  blood  corpuscles. — The  average  number  of  red 


1 6  DISEASES   OF   THE    BLOOD. 

blood  corpuscles  is,  in  the  healthy  adult  male,  5,000,000,  and  in  the 
healthy  adult  female,  4,500,000  per  cubic  millimetre. 

In  all  forms  of  anaemia  and  in  all  cases  in  which  anaemia  is 
actually  present,  some  cases  of  slight  chlorosis  excepted,  the  red 
blood  corpuscles  are  diminished  in  number.  The  degree  of  diminu- 
tion varies  with  the  form  of  anaemia  and  the  severity  of  the  case. 
In  chlorosis,  the  diminution  is  in  the  great  majority  of  cases  com- 
paratively slight.  In  pernicious  anaemia,  on  the  other  hand,  the 
degree  of  diminution  is  extremely  great. 

The  total  amount  of  haemoglobin. — In  normal  blood,  the  total 
amount  of  haemoglobin  as  estimated  by  the  haemoglobinometer 
should  be  100  per  cent. ;  but  as  a  matter  of  fact  I  rarely  find  that  it 
is  possible  by  means  of  Govvers'  instrument  to  obtain  a  higher  per- 
centage than  85  to  90  per  cent.  In  all  forms  of  profound  anaemia 
the  total  amount  of  haemoglobin  is  diminished,  but  the  degree  of 
diminution  varies  considerably  in  different  cases. 

The  relative  richness  of  the  individual  corpuscles  in  haemoglobin. 
— This  is  a  most  important  point,  for,  as  I  have  already  stated,  in 
some  cases  of  anaemia  the  red  blood  corpuscles  are  proportionately 
much  more  diminished  than  the  haemoglobin,  while  in  other  cases 
the  haemoglobin  is  proportionately  much  more  diminished  than  the 
red  corpuscles. 

In  chlorosis,  the  anaemia  is  chiefly  due  to  diminution  of  the 
haemoglobin.  Even  in  cases  of  severe  chlorosis  the  diminution 
of  the  red  corpuscles  may  be  comparatively  slight.  In  a  case 
of  well-marked  chlorosis,  for  example,  which  was  recently  under 
observation,  the  red  blood  corpuscles,  instead  of  numbering 
4,500,000,  were  3,000,000;  while  the  haemoglobin,  instead  of  being 
85  to  90  per  cent,  (as  estimated  by  Gowers'  instrument)  only 
amounted  to  25  per  cent. 

In  this  case  of  chlorosis  the  condition  of  the  blood  would  there- 
fore be  represented  by  the  following  formula  : — 

H.  (Percentage  of  Haemoglobin)  _25 ^ 

R.C  (Percentage  of  Red  Corpuscles)    60 

But  since  Gowers'  instrument  reads  low — say  85  to  90  per  cent, 
instead  of  100  per  cent. — the  amount  of  haemoglobin  actually 
present  would  be  28  per  cent. 

Further,  since  the  average  number  of  red  blood  corpuscles  in  the 
female  is  4,500,000  (not  5,000,000),  the  3,000,000  red  corpuscles  —  66 
and  not  60  per  cent.  Hence  the  fraction  should  be  -  •  The  re- 
lative richness  of  the  individual  red  corpuscles  was  consequently  in 
this  case  less  than  half;  in  other  words,  the  colour-index  was  .42. 

In  pernicious  anaemia,  on  the  other  hand,  the  individual  red 


AN/EMIA.  17 

blood  corpuscles  may  contain  an  excess  of  haemoglobin.  In  a  case 
which  was  recently  under  my  observation,  the  red  corpuscles  were 
reduced  from  5,000,000  to  1,1 2 5, 000  =  about  25  per  cent,  (the  patient 
was  a  male),  and  the  haemoglobin  (as  registered  by  Gowers'  instru- 
ment) equalled  31  per  cent.  In  this  case  of  pernicious  anaemia  the 
condition  of  the  blood  would  therefore  (without  correction)  be  repre- 
sented by  the  fraction  ^=~  ;  but  allowing  for  the  low  reading  of 
Gowers'  instrument,  the  individual  corpuscular  richness  of  haemo- 
globin was  in  reality  greater  than  this  fraction  represents.  It  ought 
to  be  34.4  instead  of  31  per  cent. — ^=| ;  in  other  words,  the 
colour  index  was  1.3. 

The  size  and  shape  of  the  red  blood  corpuscles. — In  health,  the  red 
blood  corpuscles  are  non-nucleated,  bi-concave,  circular  discs  of  a 
pale  yellow  colour.     They  go  into  rouleaux  with  great  readiness. 

In  some  cases  of  anaemia,  more  especially  in  those  cases  in 
which  the  red  corpuscles  are  greatly  diminished  in  number,  and  in 
which  there  is  marked  poikilocytosis,  as  in  most  cases  of  pernicious 
anaemia  for  example,  the  rouleaux  formation  is  often  completely 
absent. 

In  some  cases  of  anaemia  in  which  the  red  blood  discs  are  greatly 
diminished  in  number,  as  for  example  in  pernicious  anaemia,  the  red 
corpuscles  usually  present  very  marked  alterations  in  size  and  shape 
— some  are  larger,  some  smaller  than  normal,  while  many  of  them 
are  misshaped  (poikilocytosis). 

In  other  cases  of  anaemia,  more  especially  in  those  cases  in 
which  the  red  blood  corpuscles  are  only  slightly  diminished  in 
number,  as  in  most  cases  of  chlorosis,  though  the  corpuscles  are 
paler  than  normal  they  may  present  little  or  no  alteration  in  size 
and  shape. 

The  average  diameter  of  the  normal  red  blood  corpuscle  varies 
from  7  to  8  micromillimetres  (7/z.  to  8/x.). 

Unusually  large  red  corpusles  (inegalocytes)  measuring  from  9/^.  to 
12/x.  or  even  larger  are  seen  in  various  forms  of  profound  anaemia, 
but  especially  in  pernicious  anaemia;  hence  they  are  of  some  though 
not  perhaps  per  se  of  any  great  diagnostic  importance.  Their  exact 
significance  has  not  been  definitely  determined.  By  some  authori- 
ties they  are  supposed  to  be  imperfectly  formed  red  corpuscles,  by 
others  degenerated  red  corpuscles. 

Unusually  small  red  corpuscles {inicrocytes)  measuring  in  diameter 
from  2jj-.  to  5/x.  or  even  less  also  occur  in  a  variety  of  circumstances  ; 
they  occur  after  extensive  haemorrhages  and  are  present  in  advanced 
conditions  of  blood  degeneration,  notably  in  pernicious  anaemia  ; 
they  are  suggestive  of  very  rapid  and  imperfect  blood  formation, 

B 


1 8  DISEASES   OF   THE   BLOOD. 

which  may  either  be  the  result  of  increased  blood  destruction  with 
(consequently)  too  rapid  formation,  or  of  a  primary  defect  or  lesion 
in  the  blood-forming  organs — especially  the  marrow  of  the  bones. 

Small  red  corpuscles,  distinguished  from  the  last  by  their  deeper 
colour,  and  known  under  the  term  of  Eichhorst's  corpuscles,  are 
highly  suggestive  though  perhaps  not  pathognomonic  of  pernicious 
anaemia.  So  far  as  my  observation  enables  me  to  judge,  they  only 
occur  in  a  small  proportion  of  cases  of  pernicious  anaemia. 

Irregularity  in  the  shape  of  the  red  blood  corpuscles  (poikilo- 
cytosis)  occurs  in  many  conditions,  but  more  especially  in  cases  in 
which  the  blood  corpuscles  are  excessively  reduced  in  number,  in 
which  the  blood  is  very  watery  and  in  which  the  formation  of  the 
red  blood  corpuscles  is  being  carried  on  too  rapidly  or  in  an  im- 
perfect manner.  By  some  authorities  these  irregularly  formed 
corpuscles  are  regarded  as  degenerated  red  corpuscles,  but  I  am 
strongly  disposed  to  think  that  they  are  imperfectly  formed  red 
corpuscles. 

Dr  Robert  Muir  tells  me  that  in  those  cases  of  anaemia  in  which 
the  red  corpuscles  present  marked  alterations  in  size  he  has  found 
that  the  nucleated  red  corpuscles  in  the  bone-marrow  also  show 
greater  variations  in  size  than  in  the  normal  condition — a  condition 
corresponding  with  that  which  obtains  in  the  foetus. 

Marked  alterations  in  size  and  shape  of  the  red  blood  corpuscles 
are,  as  we  shall  afterwards  see,  suggestive  of  pernicious  anaemia. 

Nucleated  red  blood  corpuscles  occasionally  occur,  more  especially 
in  spleno-medullary  leucocythaemia  and  in  some  cases  of  pernicious 
anaemia  ;  but  they  cannot  be  satisfactorily  seen  without  staining 
reagents.  These  nucleated  corpuscles  vary  in  size.  They  are  espe- 
cially frequent  in  spleno-medullary  leucocythaemia  and  in  children 
affected  with  profound  anaemia.  They  represent  the  passage  of 
the  red  corpuscles  into  the  blood  stream  before  they  have  lost 
their  nuclei,  and  are  probably  indicative  of  an  excessive  and  imper- 
fect blood  formation — an  effort  on  the  part  of  Nature  to  compensate 
for  the  increased  corpuscular  destruction  ;  this  view  is  confirmed 
by  the  fact  that  nucleated  red  corpuscles  may  readily  be  made  to 
appear  in  the  blood  of  animals  by  bleeding  them,  as  Dr  Robert 
Muir  and  others  have  shown. 

The  number,  size,  and  microscopic  characters  of  the  different  forms 
of  white  blood  corpuscles. — In  many  cases  of  anaemia  there  is  little  or 
no  change  in  the  white  corpuscles.  A  slight  or  moderate  increase 
in  the  number  of  white  blood  corpuscles  is  met  with  in  a  great 
variety  of  different  conditions,  such  as  suppuration,  inflammatory 
lesions,  and  in  some  forms  of  fever.     In  leucocythaemia,  the  number 


ANAEMIA.  19 

of  white  blood  cells  may  be  greatly  increased  ;  instead  of  being 
8,000  per  cubic  millimetre,  which  is  about  the  normal  average  in 
health,  they  may  number  400,000  or  more  per  cubic  millimetre  ; 
instead  of  being  in  the  proportion  of  1  to  400  or  500  red  blood 
corpuscles  as  they  usually  are  in  health,  they  may  number  I  to  50 
or  less.  In  leukaemia  or  leucocythsemia  it  is  by  no  means  un- 
common to  find  one  white  corpuscle  to  every  4  or  5  red  cells,  and 
it  is  said  that  in  rare  cases  the  white  blood  cells  may  be  as  numerous 
as  the  red.  In  estimating  the  number  of  white  corpuscles  which 
are  present,  the  actual  number  per  cubic  millimetre  should  be 
taken  ;  the  older  method  of  estimating  the  proportion  of  white 
to  red  corpuscles  is  fallacious  (for  the  red  corpuscles  are  often 
diminished  in  number)  and  should  be  discontinued. 

Recent  methods  of  observation — the  examination  of  dried  and 
stained  specimens — have  shown  that  several  different  forms  of 
white  blood  corpuscles  are  normally  present  in  the  blood.  The 
more  important  forms  are  : — 

1.  Small  uninucleated  corpuscles  {lymphocytes')  measuring  about 
7/x.  to  9^.  in  diameter.  The  nucleus  is  relatively  very  large,  the 
protoplasm,  which  does  not  contain  granules,  merely  consisting  of 
a  narrow  rim  round  the  nucleus.  In  normal  blood  they  usually 
equal  about  25  per  cent,  of  the  total  white  corpuscles. 

2.  Large  tminuclear  leucocytes. — These  are  considerably  larger 
than  the  red  blood  corpuscles,  measuring  up  to  12//..  ;  their  nuclei  are 
larger  than  the  nuclei  of  the  small  uninucleated  leucocytes ;  the 
protoplasm  is,  relatively  to  the  nucleus,  abundant  and  non-granu- 
lated. 

3.  Transitional  forms  between  2  and  3. 

The  large  nucleated  and  transitional  forms  of  the  uninucleated 
corpuscles  usually  constitute  from  3  to  6  per  cent,  of  the  total 
leucocytes  in  normal  blood. 

4.  Large  polymorpJwnuclear  {imdtinucleated  or  multipartite- 
nuclear)  corpuscles — Ehrliclis  neutrophiles— -Most  of  them  measuring 
from  9/x.  to  10/x.  in  diameter,  some  being  larger  (13/x.  to  14/*.). 
The  protoplasm  is  finely  granular.  These  are  the  most  numerous 
form  ;  in  normal  blood  they  usually  equal  about  65  to  70  per  cent, 
of  the  whole  white  corpuscles. 

5.  Large  leucocytes,  with  one  or  more  nuclei,  containing  coarse 
granules  which  stain  deeply  with  eosin,  hence  they  are  termed 
eosinophile  cells.  In  normal  blood  they  usually  equal  about  \  to  4 
per  cent,  of  the  total  leucocytes.  Ehrlich,  to  whom  we  are  so 
greatly  indebted  for  our  knowledge  of  the  different  characters  of 
the  leucocytes  and  the  way  in  which  they  react  to  different  staining 


20  DISEASES   OF   THE   BLOOD. 

agents,  originally  thought  that  an  increase  of  these  eosinophile 
cells  was  indicative  of  myelogenic  leucocythaemia  ;  but  this  view 
seems  now  to  have  been  quite  abandoned  by  all  authorities. 

In  cases  of  anaemia  in  which  the  leucocytes  are  greatly  increased 
{i.e.,  cases  of  leukaemia  or  leucocythaemia)  the  character  of  the 
leucocytes  and  the  relative  proportion  of  the  different  forms  vary 
greatly. 

These  differences  are  manifested  not  only  by  the  size  of  the 
leucocytes  and  the  character  of  their  contained  nuclei,  but  also  by 
the  way  in  which  the  white  blood  corpuscles  react  to  various  stains. 
I  shall  return  to  this  point  when  I  come  to  describe  leucocythaemia. 
All  I  need  say  now  is,  that  in  some  cases  of  leucocythaemia,  the 
splenic  or  spleno-medullary  form  of  leucocythaemia  as  it  is  now 
generally  termed,  several  different  forms  of  white  corpuscles  are 
usually  present ;  but  the  chief  alteration  consists  in  the  presence  in 
the  blood  of  large  iminucleated  corpuscles,  which  measure  from  1 2^. 
to  20//.,  and  which  do  not  contain  eosinophile  granules  ;  some  of 
these  cells  seem  to  be  identical  with  marrow  cells,  hence  they  have 
been  termed  myelocytes ;  in  some  cases  the  eosinophile  cells,  which 
are  present  in  normal  blood  in  small  proportion  Q  to  4  per  cent,  of 
the  total  leucocytes),  may  be  greatly  increased,  but  this  alteration 
is  inconstant.  Whereas  in  other  cases  of  leucocythaemia  (in  which 
the  spleen  is  often  also  greatly  enlarged  and  in  which  the  lymphatic 
glands  are  usually  but  not  always  enlarged)  the  increase  of  the 
white  corpuscles  is  for  the  most  part  (some  authorities  say  almost 
entirely)  due  to  an  enormous  increase  of  the  uninucleated  white 
corpuscles  of  small  size  (the  lymphocytes)  which  are  normally 
present  in  the  blood.  Hence  these  cases  have  been  termed  cases 
of  lymphatic  leucocythaemia. 

Blood-plates  or  blood-platelets. — These  are  the  smallest  formed 
elements  of  normal  blood.  They  are  circular  or  oval  in  form  with 
a  well-defined  margin,  and  they  consist  of  a  highly  refractile  plasmic 
material.  Their  usual  size  is  from  I  to  3  micromillimetres  in 
diameter  ;  they  vary  in  number  from  125,000  to  250,000  per  cubic 
millimetre  (some  writers  say  300,000  or  even  more).  They  seem  to 
be  most  numerous  in  cachectic  conditions,  after  long-continued 
bleeding,  etc.  In  pernicious  anaemia  they  are  usually  (and  some- 
times markedly)  diminished.  Hayem  regards  them  as  immature  red 
blood  corpuscles  ;  according  to  other  authorities  they  are  the  result 
of  blood  destruction.  They  seem  to  be  the  active  agents  in  the 
process  of  coagulation  and  the  formation  of  coagula  (especially  white 
thrombij.  Dr  Robert  Muir  tells  me  that  he  has  "  found  that  there  is 
no  relationship  between  the  number  of  the  blood-plates  and  the  rate 


AN.EMIA.  21 

of  blood  formation.  After  a  large  haemorrhage  followed  by  rapid 
regeneration  and  no  cachexia  their  number  was  little  increased. 
Whereas  after  several  haemorrhages  with  the  development  of  some 
general  cachexia  and  impairment  of  blood  regeneration  their 
number  was  sometimes  very  great."  He  thinks  that  probably  the 
impoverished  condition  of  the  serum  is  the  chief  condition  associated 
with  their  increase. 

Max  Schultze's  granular  masses  are  irregular  bodies  composed 
of  colourless  granular  protoplasm  ;  they  seem  to  consist  of  collec- 
tions of  blood-platelets  or  perhaps  of  broken-down  leucocytes. 

From  these  statements,  it  will  be  seen  that  the  exact  characters 
of  the  blood  vary  considerably  in  different  forms  of  anaemia. 
Speaking  generally,  three  great  groups  of  anaemia  may  be  described, 
namely  : — 

i .  Cases  in  which  the  red  blood  corpuscles  and  the  Juzmoglobin  are 
diminished  in  the  same  proportion. — In  these  cases,  the  chief  change 
is  a  watery  condition  of  the  blood,  a  hydraemia.  The  term  oligaemia, 
which  literally  means  deficiency  of  the  blood  as  a  whole,  has  been 
applied  to  this  form  of  anaemia.  It  is  characteristic  of  many  of 
the  secondary  forms  of  anaemia  (anaemia  due  to  haemorrhage, 
wasting  discharges,  etc.). 

2.  Cases  of  ancemia  in  zvhich  the  hcenioglobin  is  proportionally 
much  more  diminished  than  the  red  blood  corpuscles. — This  condition 
is  highly  characteristic  of  chlorosis,  though  it  also  occurs  in  other 
conditions.  Dr  Stephen  Mackenzie  has  also  shown  that  it  occurs 
in  some  cases  of  cancer,  and  my  own  observations  confirm  his 
views  on  this  point. 

3.  Cases  of  ancemia  in  zvhich  the  red  blood  corpuscles  are  more 
diminished  than  the  hcemoglobin. — This  condition  occurs  in  pernicious 
anaemia,  rarely  if  ever,  so  far  as  we  know,  in  other  conditions. 

Let  us  now  consider  some  of  the  more  important  forms  of 
primary  anaemia  individually  and  in  detail. 


CHLOROSIS. 

Definition  or  Short  Description. — This  disease,  to  which  the 
synonyms  chloreemia,  chloranazmia,  green  sickness,  etc.,  have  been 
applied,  is  by  far  the  most  common  form  of  primary  anaemia.  It 
varies  very  greatly  in  severity  in  different  cases.  It  is  characterised 
by  all  the  typical  symptoms  of  profound  anaemia — weakness,  pallor, 
shortness  of  breath,  palpitation,  giddiness,  etc.  The  essential  blood 
change  is  a  marked  deficiency  of  haemoglobin  ;  and  since  in  the 
great  majority  of  cases  the  red  blood  cells  are  comparatively  little 
diminished  in  number,  the  richness  of  the  individual  red  blood 
corpuscles  in  haemoglobin  (as  well  as  the  total  amount  of  haemo- 
globin in  the  blood)  is  markedly  below  the  normal.  In  the  vast 
majority  of  cases  the  disease  is  rapidly  cured  by  the  administration 
of  iron. 

Etiology. 

Age  and  Sex. — Chlorosis  is  essentially  a  disease  of  the  female, 
and  in  the  vast  majority  of  cases  is  developed  at  or  about  the  time 
of  puberty  ;  but  cases  of  apparently  causeless  anaemia,  in  which  the 
blood  presents  all  the  characters  of  chlorosis  and  which  are  curable 
by  iron,  are  sometimes  met  with  in  older  women.  Cases  which 
appear  to  be  closely  allied  to  (and  in  some  cases  apparently 
identical  with)  chlorosis  are  also  occasionally  met  with  in  children, 
and  also  perhaps  in  men,  though  some  authorities  doubt  whether 
true  chlorosis  ever  occurs  in  adult  males. 

In  314  typical  cases  of  chlorosis  of  which  I  have  notes,  the  ages 
were  as  follows  : — 


Table  i. 


Years. 
12 
13 
14 

'5 
16 

17 
18 

'9 
20 
21 

T> 


-Showing  the  Age  in  314  Cases  of  Chlorosis. 

No.  of  Cases. 


IO 

9 
9 


No.  of  Cases. 

Years 

I 

24 

I 

25 

6 

26 

6 

27 

19 

28 

3i 

29 

4i 

3° 

47 

3' 

39 

32 

33 

33 

18 

23 

Total 


3H 


CHLOROSIS. 


^3 


The  result  of  this  analysis  is  graphically  represented  in  Fig.  1  ; 
the  curve  is  a  very  remarkable  one.  The  apex  corresponds  to  the 
19th  year,  the  rise  and  fall  on  each  side  of  this  point  being 
singularly  symmetrical. 

Of  my  314  cases,  251  occurred  between  the  ages  of  16  and  23 
inclusive  ;  but  it  must  be  remembered  that  this  does  not  represent 
the  age  at  which  the  disease  commenced,  but  the  age  at  which  the 
patients  came  under  my  obser- 
vation. In  many  of  the  cases  the 
patients  had  suffered  from  the 
disease  for  several  months  or 
years  before  I  saw  them.  Hence 
the  average  age  at  which  the 
disease  commenced  in  these  cases 
was  certainly  somewhat  lower 
than  is  shown  in  the  table.  But 
there  is  little  doubt  that  in  the 
great  majority  of  cases  of  chlorosis 
the  disease  develops  between  the 
ages  of  15  and  23 ;  comparatively 
few  cases  are  met  with  before 
the  age  of  15  or  after  the  age  of 
24  ;  and  in  most  of  the  cases 
which  are  met  with  after  the  age 
of  24,  the  disease  commenced 
at  an  earlier  period  of  life. 

Occupation,  locality,  etc. — 
The  disease  occurs  amongst  all 
classes  of  society,  but  in  my 
experience  it  is  most  common  in 
young  servant  girls.  Sedentary 
habits,  want  of  exercise,  want  of 
fresh  air  and  sunlight,  late  hours, 
excessive  fatigue,  over-pressure 
at  school,  mental  anxiety,  pro- 
longed grief,  home-sickness,  etc., 

undoubtedly  seem  in  some  cases  to  predispose  to  its  production  ; 
but  in  other  cases  these  factors  seem  to  be  wanting.  The  disease 
appears  to  be  more  common  in  towns  than  in  the  country. 
Country  girls  who  come  into  service  in  town  are,  it  is  said,  par- 
ticularly apt  to  be  affected. 

Influence  of  heredity. — In  some  families  there  appears  to  be 
a  hereditary  tendency  to  the  disease  ;  and  many  authorities  are 


Age 

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5  16  17,T3  U  20  212223 

24  2i26  27  28l29.30.31 

32  33 

Fig.  I. — Graphic  Representation  of  the  Age 
Frequency  of  314  Cases  of  Chlorosis. 


24  DISEASES   OF   THE   BLOOD. 

agreed  that  there  is  a  certain  relationship  between  tuberculosis  and 
chlorosis ;  in  other  words,  it  would  appear  that  in  families  predisposed 
to  tuberculosis  the  girls  have  a  stronger  tendency  to  chlorosis  than 
the  girls  of  other  families  in  which  there  is  no  tubercular  tendency. 
An  analysis  of  my  own  cases  gives  some  support  to  this  view. 

In  the  80  cases  included  in  Table  2,  the  details  of  the  family 
history  are  stated  in  72  cases.  In  these  72  cases,  there  was  a 
definite  history  of  some  tubercular  affection  in  the  near  relatives 
(parents,  brothers  and  sisters,  uncles  and  aunts)  in  22  cases  or  30 
per  cent. 

But  it  is  probable  that  these  figures  do  not  exactly  represent  the 
tubercular  tendencies  of  patients  affected  with  chlorosis,  and  that 
for  the  following  reasons  : — ■ 

On  the  one  hand,  in  many  of  the  cases  in  which  no  definite 
tubercular  history  could  be  elicited,  it  was  stated  that  some  near 
relative  was  delicate,  but  the  exact  cause  of  the  delicacy  could  not 
be  ascertained  ;  no  doubt  in  a  certain  proportion  of  these  cases  the 
ill  health  was  due  to  tubercle.  Again,  in  a  considerable  proportion 
of  the  cases  in  which  no  tubercular  history  in  the  near  relatives  was 
elicited,  the  exact  cause  of  death  of  some  of  the  near  relatives 
(parents,  brothers,  sisters,  etc.)  was  unknown  to  the  (chlorotic) 
patients  ;  in  a  certain  number  of  these  cases  death  was  no  doubt 
due  to  tubercle. 

On  the  other  hand,  the  80  cases  included  in  the  Table  were  all 
hospital  patients,  in  whom  the  mortality  from  tubercular  diseases 
is  somewhat  greater  than  in  the  average  population,  and  certainly 
greater  than  in  the  more  fortunately  situated  ranks  of  society. 

Theories  as  to  the  cause  of  chlorosis. — The  exact  causation 
of  chlorosis  has  given  rise  to  a  great  deal  of  difference  of  opinion. 

It  used  to  be  thought  that  the  disease  was  due  to  disappointment 
in  love  ;  and  there  can  be  no  doubt  that  mental  anxiety  and  grief 
may  act  as  contributory  or  exciting  causes,  but  only  perhaps  in 
persons  predisposed  to  chlorosis  or  already  suffering  from  it. 

Derangement  or  disease  of  the  uterus  and  ovaries  has  been 
suggested  as  a  cause.  Amenorrhoea  is  usually  present  in  severe 
cases  of  chlorosis,  but  it  appears  to  be  the  result,  not  the  cause,  of 
the  disease.  Proof  of  this  is  found  in  the  fact  that  in  a  not  incon- 
siderable proportion  of  well-marked  cases  the  menstruation  is 
perfectly  regular.  It  is  true  that  in  many  of  the  cases  of  chlorosis 
in  which  the  menstruation  is  regular  in  time,  the  discharge  is 
deficient  in  quantity  and  too  pale  in  colour;  but  in  some  cases,  thev 
menstruation  is  perfectly  natural  in  every  respect.  In  rare  cases, 
there  is  menorrhaena. 


CHLOROSIS.  25 

But  although  amenorrhoea  is  not  the  cause  of  chlorosis,  there 
can,  I  think,  be  little  doubt  that  the  active  strain  which  is  thrown 
upon  the  tissues  and  organs  of  the  female  at  the  time  of  puberty 
and  during  the  first  few  years  of  menstrual  life  is  an  important 
factor  in  the  production  of  the  disease.  According  to  Niemeyer, 
chlorosis  is  invariably  developed  in  girls  who  begin  to  menstruate 
before  the  mammas  and  genital  organs  are  developed.  My  own 
view  is  that  the  unusual  strain,  so  to  speak,  which  is  thrown  upon 
the  blood-forming  organs  by  the  rapid  development  of  the  tissues 
and  organs  which  occurs  at  the  time  of  puberty,  and  especially  by 
the  development  and  establishment  of  the  function  of  menstruation, 
is  a  most  important  factor  in  the  production  of  the  condition.  This 
view  seems  to  me  to  be  supported  by  the  fact  that  as  the  patient 
gets  older  (in  other  words,  as  the  organism  becomes  accustomed  to 
the  strain  on  the  blood-forming  organs  which  menstruation  entails) 
the  disease  and  the  tendency  to  relapse  which  is  such  a  striking 
feature  of  the  disease  gradually  disappear. 

Virchow  thought  that  chlorosis  was  due  to  defective  develop- 
ment of  the  aorta  and  arterial  system  ;  but  narrowing  of  the  aorta 
and  thinness  of  the  arterial  coats  are  not  always  present ;  in  some 
cases  they  are  perhaps  the  result  and  not  the  cause  of  the  chlorosis  ; 
or  perhaps  the  narrowing  of  the  aorta  and  thinness  of  the  arteries 
and  the  chlorosis  are  the  result  of  a  common  cause — a  congenital 
or  developmental  condition,  i.e.,  some  imperfection  in  the  develop- 
ment of  the  blood-forming  organs  and  blood  vascular  system. 
Further,  as  Stockman  has  pointed  out,  Virchow's  theory  seems 
contradicted  by  the  fact  that  cases  of  chlorosis  are  rapidly  cured 
by  appropriate  treatment. 

Trousseau  and  others  have  suggested  that  the  primary  cause  is 
a  nervous  derangement  which  produces  alterations  in  the  blood  ; 
this  may  be  so,  but  there  can  I  think  be  little  doubt  that  many  of 
the  nervous  symptoms  which  are  so  frequently  associated  with  the 
disease  are  a  result  rather  than  the  cause  of  the  bloodlessness  ;  this 
is  not,  of  course,  an  argument  against  the  (primary)  nervous  origin 
of  the  disease.  Cases  such  as  that  mentioned  by  Clifford  Allbutt, 
in  which  a  profound  degree  of  chlorosis  was  developed  (or  rather 
redeveloped,  for  the  patient  had  just  recovered  from  the  disease) 
after  a  nervous  shock,  lend  some  support  to  the  view  that  the 
bloodlessness  is  the  result  of  a  trophic  nerve  change  acting  either 
directly  on  the  blood-forming  organs,  or  indirectly  on  the  blood  by 
the  production  perhaps  of  some  toxic  product  of  metabolism;  but 
as  yet  there  are  not,  so  far  as  I  know,  any  definite  facts  in  favour 
of  such  a  mode  of  causation.     Further,  the  condition  of  the  blood 


26  DISEASES   OF   THE    BLOOD. 

in  cases  of  chlorosis  seems  strongly  opposed  to  the  view  that  the 
anaemia  is  the  result  either  of  the  defective  production  of  red 
corpuscles,  or  of  a  destruction  of  red  blood  corpuscles  due  to  a 
toxic  agent. 

Sir  Andrew  Clark  supposed  that  chlorosis  was  the  result  of 
auto-intoxication  from  the  intestine  (copr?emia)  due  to  constipa- 
tion. Constipation  is  certainly  very  common  in  cases  of  chlorosis, 
but  it  is  by  no  means  always  present.  In  quite  a  number  of  well- 
marked  cases  which  have  come  under  my  own  observation,  more 
especially  amongst  girls  belonging  to  the  upper  orders  of  society, 
constipation  has  been  entirely  absent.  In  some  of  these  cases,  I 
have  satisfied  myself  that  the  bowels  were  not  only  opened,  but 
sufficiently  freely  opened,  every  day.  It  must,  however,  be  re- 
membered that  auto-intoxication  from  the  intestine  may  probably 
occur  even  when  there  is  no  constipation.  That  constipation  may 
in  some  cases  have  an  influence  in  the  production  of  the  disease 
is  I  think  highly  probable,  but  it  cannot  be  regarded  as  the  essential 
and  fundamental  cause.  Further,  Rethers  *  and  Mornerf  claim 
that  their  analyses  of  the  urine  in  cases  of  chlorosis  show  that  there 
is  no  evidence  of  excessive  sepsis  in  the  alimentary  canal.  Again, 
if  intestinal  sepsis  and  auto-intoxication  were  the  cause,  the  disease 
ought  to  occur  in  men  and  to  be  frequently  developed  in  women 
during  the  middle  and  later  periods  of  adult  life  ;  but  this  is  not 
the  case. 

It  has  also  been  theorised  that  chlorosis  is  due  to  deficiency  of 
hydrochloric  acid  in  the  gastric  juice  and  the  presence  of  an  excess 
of  sulphuretted  hydrogen  in  the  intestines,  and  that  these  condi- 
tions produce  the  disease  by  interfering  with  the  assimilation  of 
iron. 

Bunge  I  in  particular  has  advocated  the  view  that  the  presence 
of  an  excess  of  sulphuretted  hydrogen  and  of  alkaline  sulphides  in 
the  intestinal  tract  produces  a  continuous  non-assimilation  of  iron 
by  combining  with  the  organic  iron  of  the  food  and  forming  an 
inorganic  and  therefore  insoluble  iron  compound  ;  and  that  the 
chlorotic  condition  results  from  the  non-assimilation  of  iron  pro- 
duced in  this  way.  But  in  opposition  to  this  view  it  has  been  shown 
by  Rethers  and  Morner  (a)  that  there  is  no  increase  of  aromatic 
sulphates  in  the  urine  of  chlorotics,  and  therefore  no  indication  of 
excessive  putrefaction  in  the  intestine  ;  and  by  Stockman  §  (b)  that 

*  Dissertation,  Berlin,  1891. 

t  Zeitschr.  f.  Physiol.  Chemie,  xviii.  1893. 

X   Lehrbuch  der  Physiolog.  und  Patholog.  Chemie,  1887. 

S  "  British  Medical  Journal,"  1893,  Vol.  i.,  pp.  881  and  942. 


CHLOROSIS.  27 

the  administration  of  sulphide  of  iron  (enclosed  in  keratin  capsules, 
so  as  to  ensure  its  reaching  the  intestine)  is  capable  of  curing 
chlorosis  ;  and  (V)  that  other  drugs,  such  as  bismuth,  which  are  as 
capable  of  neutralising  sulphuretted  hydrogen  in  the  intestine  as 
iron  is,  do  not  cure  the  disease. 

Ulceration  of  the  stomach  and  gastric  haemorrhage  have  been 
suggested  as  causes  of  the  disease  ;  possibly  these  conditions  may 
in  some  cases  act  as  predisposing  causes,  and  they  may,  of  course, 
undoubtedly  aggravate  the  anaemia  when  they  happen  to  be  asso- 
ciated with  chlorosis  ;  but  there  can  I  think  be  little  doubt  that 
in  most  cases  they  are  results  rather  than  causes  of  the  disease. 
Dilatation  of  the  stomach  and  tight-lacing  (which  is  apt  to  produce 
dilatation  of  the  stomach)  have  also  been  blamed  ;  but  here  again 
I  regard  the  dilatation  of  the  stomach  rather  as  a  consequence  than 
a  cause  of  the  disease. 

Stockman  is  of  opinion  that  the  essential  causes  of  chlorosis  are 
two,  or  possibly  three,  namely  : — 

"(1.)  Excessive  menstrual  loss,  or  (much  less  frequently)  other 
blood  loss.  This,"  he  states,  "  may  be  relative,  that  is,  too  much  for 
a  weakly  or  rapidly-growing  organism  to  bear,  or  it  may  be  actually 
large. 

"  (2.)  Insufficient  ingestion  of  iron  with  food.  Anything  which 
diminishes  the  appetite  diminishes  the  consumption  of  iron  ;  there- 
fore dyspepsia,  constipation,  heated  rooms,  insufficient  exercise, 
unhealthy  atmospheres,  mental  depression,  etc.,  all  predispose  to 
the  affection  by  lessening  the  amount  of  food  consumption.  It  is 
probably  owing  to  change  of  habits,  confinement  indoors  and  want 
of  fresh  air — all  leading  to  small  consumption  of  food — that  so  many 
girls  from  the  country  become  anaemic  on  going  into  towns  to  live. 

"  The  dyspepsia  and  constipation  which  are  so  common  in 
chlorotic  patients  lead,"  he  says,  "  to  the  consumption  of  a  totally 
inadequate  amount  of  food,  and  therefore  of  a  totally  inadequate 
amount  of  iron." 

From  an  analysis  of  the  dietaries  of  fifteen  healthy  persons,  and 
from  four  analyses  of  the  daily  dietary  of  two  girls  suffering  from 
chlorosis,  he  concludes  that  the  amount  of  iron  in  the  food  of 
chlorotic  patients  is  very  much  smaller  than  normal — about  one- 
third  only  of  that  of  healthy  persons.  Further,  he  has  shown  that 
the  quantity  and  kind  of  food  consumed  exercise  an  important 
influence  on  the  amount  of  iron  available  for  blood  formation. 

At  the  same  time,  he  admits  that  "patients  suffering  from 
chlorosis  fed  on  even  a  rich  and  varied  diet,  containing  plenty  of 
iron,  do  not,  as  a  rule,  recover  until  inorganic  iron  is  administered." 


28  DISEASES   OF   THE   BLOOD. 

He  states  that  in  a  very  large  number  of  cases  of  chlorosis 
there  is  a  combination  of  the  two  causes  just  enumerated  ;  but 
he  adds 

"(3.)  It  is  possible  that  certain  persons  are  born  inherently  weak 
in  blood-forming  power  and  tend  to  become  anaemic  under  very 
slight  provocation." 

Stockman's  observations  as  to  the  amount  of  iron  in  the  food  of 
chlorotics  are  highly  suggestive  and  important ;  but  it  seems  to  me 
that  further  observation  and  a  much  more  extended  series  of  analyses 
are  required  before  they  can  be  applied  to  chlorotics  as  a  whole,  i.e., 
before  we  can  definitely  conclude  that  in  all  cases  of  chlorosis  the 
iron  in-take  is  insufficient. 

And  even  if  it  be  allowed  that  the  iron  "in-take"  is  deficient 
in  all  well-marked  cases  of  chlorosis,  it  does  not  follow  that  this  is 
one  of  the  chief  causes  of  the  disease.  It  does  not  follow,  because 
in  well-marked  cases  of  chlorosis  and  in  the  advanced  stages  of  the 
disease  the  iron  "  in-take  "  is  insufficient,  that  the  iron  "  in-take  "  is 
deficient  in  the  pre-chlorotic  period,  as  it  may  be  termed,  and  in  the 
earlier  stages  of  the  disease.  The  deficient  iron  "  in-take  "  in  the 
advanced  stages  may  be  the  result  of  the  disease,  i.e.,  of  the  defective 
appetite  and  dyspeptic  conditions  which  are  due  to  the  chlorosis. 
It  seems  premature  to  conclude  that  one  of  the  chief  causes  of 
chlorosis  is  a  deficient  "in-take"  of  iron,  unless  it  can  be  shown 
that  at  the  onset  of  the  disease  and  during  the  period  immediately 
preceding  the  onset  of  the  disease,  the  iron  "  in-take"  is  deficient. 

Further,  if  the  cause,  or  one  of  the  chief  causes,  of  chlorosis  is  a 
deficiency  of  iron  in  the  food,  the  chlorotic  condition  ought,  in  its 
earlier  stages  at  all  events  and  in  slight  cases,  to  be  readily  cured 
by  (1)  removing  the  dyspeptic  condition  and  by  the  administration 
of  a  liberal  (iron-containing)  diet — but  this  is  not  the  case  ;  by  (2) 
the  administration  of  small  doses  of  the  organic  compounds  of  iron 
— but  almost  all  authorities  are  agreed  that  the  organic  compounds 
of  iron  are  less  effective  than  the  inorganic  ;  and  by  (3)  the  adminis- 
tration of  small  quantities  of  iron  in  any  form — but  this  is  not  the 
case. 

Stockman  has  recently  shown  that  in  health  the  iron  "  in-take  " 
and  the  iron  "  out-put "  in  the  urine  and  faeces  are  very  small — 
in  the  cases  which  he  most  carefully  investigated  the  quantity  of 
metallic  iron  in  ordinary  dietaries  seldom  exceeded  10  milligrams 
per  diem,  and  might  be  as  low  as  6  milligrams,  in  people  of  ordinary 
appetite  and  digestion.  These  observations  seem  to  show  that  the 
amount  of  iron  which  must  be  absorbed  from  the  intestine  under 
ordinary  conditions  in  order  to   maintain  the  body  in  a  state  of 


CHLOROSIS.  29 

health  is  extremely  small  (rarely  more  than  10  milligrams  per 
diem).  Consequently,  if  chlorosis  is  due  to  a  deficient  "  in-take  "  of 
iron,  the  disease  ought  to  be  rapidly  cured  by  very  minute  doses 
of  iron — but  this  is  certainly  not  the  case,  in  most  instances  at 
least. 

Further,  as  regards  loss  of  blood,  it  must  be  remembered  that 
chlorosis  is  sometimes  developed  in  girls  who  have  never  menstruated, 
and  that  in  a  large  proportion  of  cases  of  chlorosis  menstruation 
(though  perhaps  it  may  be  relatively  excessive  and  too  much,  as 
Stockman  states,*  for  a  weakly  or  rapidly-growing  organism  to  bear) 
is  much  less  profuse  than  normal — I  refer,  of  course,  to  the  con- 
dition of  menstruation  at  the  onset  of  the  disease  and  not  to  the 
condition  of  menstruation  when  the  disease  is  thoroughly  estab- 
lished ;  for  in  the  majority  of  cases  of  chlorosis  at  this  stage, 
amenorrhcea  is  present. 

Lloyd  Jones  concludes,  as  the  result  of  a  long  series  of  observa- 
tions on  the  blood  in  normal  girls  and  chlorotic  patients,  that 
"  chlorosis  is  an  exaggeration  of  a  physiological  blood  condition,  an 
exaggeration  of  a  change  which  occurs  in  the  blood  of  healthy- 
females  at  puberty,  and  which  shows  itself  in  many  females  at  each 
menstrual  period.  Further,  he  suggests  that  appearances  point  to 
the  likelihood  of  chlorosis  being  a  chronic  auto-intoxication  brought 
about  by  some  substances  which  are  possibly  the  products  of  uterine, 
Fallopian,  or  ovarian  metabolism,  and  which  produce  their  effects 
on  the  blood  by  inducing  changes  in  the  gastro-intestinal  canal  by 
the  medium  of  the  nervous  system."  f 

As  I  have  already  stated,  the  essential  clinical  feature  of 
chlorosis  is  a  diminution  of  the  haemoglobin — a  deficiency  of  the 
iron  of  the  blood.  Further,  in  order  to  understand  the  causation  of 
the  disease  it  must  be  remembered  : — (a)  that  chlorosis  is  essen- 
tially a  disease  of  the  female  sex  ;  (b)  that  it  is  in  the  vast  majority 
of  cases  developed  at  or  about  the  period  of  active  sexual  develop- 
ment ;  and  (c)  that  in  the  great  majority  of  cases  it  is  speedily  and 
easily  cured  by  the  administration  of  iron — provided  only  that  the 
iron  is  given  in  sufficiently  large  quantities  and  that  the  gastro- 
intestinal tract  and  its  contents  are  in  a  condition  to  permit  of  the 
absorption  of  the  remedy. 

There  seem  to  be  no  sufficient  reasons  for  supposing  that  the 
deficiency  of  haemoglobin  in  the  blood  which  is  the  essential  feature 
of  chlorosis  is  primarily  due  to  defective  action  of  the  blood-forming 


*  "British  Medical  Journal,"  14th  December  1895. 
t  "  Chlorosis,"  by  Dr  E.  Lloyd  Jones,  p.  56. 


30  DISEASES   OF   THE   BLOOD. 

organs  properly  so  called  (the  marrow  of  the  bones,  etc.).  This 
view  seems  supported  by  the  following  facts  : — 

That  in  the  earlier  stages  of  the  disease  and  in  slight  cases  of 
chlorosis  the  only  alteration  in  the  blood  is,  practically  speaking, 
a  deficiency  of  haemoglobin  ;  the  red  corpuscles  may  be  little  if  at 
all  reduced  in  number,  and  they  may  present  little  or  no  alterations 
in  size  and  shape  ;  and 

That  there  appears  to  be  no  inability  on  the  part  of  the  red 
blood  corpuscles  to  take  up  iron,  provided  only  that  they  have  the 
chance  of  doing  so.  It  would  appear  that  in  the  earlier  stages  of 
chlorosis,  at  all  events,  the  red  corpuscles  are  normally  formed  by 
the  bone-marrow  but  are  sent  off  without  their  normal  supply  of 
haemoglobin.  The  diminution  in  the  number  and  the  alterations 
in  size  and  shape  of  the  red  corpuscles,  which  only  become  marked 
in  the  advanced  stages  of  severe  cases  of  chlorosis,  may  quite  well 
be  accounted  for  (as  my  son  Dr  Edwin  Bramwell  has  pointed  out 
to  me)  by  the  effects  which  a  long-continued  and  marked  deficiency 
of  oxygen  {i.e.,  of  haemoglobin)  produces  on  the  blood-producing 
organs. 

The  essential  cause  of  chlorosis,  then,  would  appear  to  be  a 
deficiency  of  haemoglobin  in  the  blood — a  deficiency  which  is 
produced  in  some  way  or  another  by  the  strain  which  is  put  upon 
the  tissues  and  blood-forming  organs  of  the  female  by  the  rapid 
development  which  takes  place  at  or  about  the  time  of  puberty,  and 
especially  perhaps  by  the  unusual  strain  which  the  development 
and  establishment  of  the  function  of  menstruation  entail.  Further, 
functional  derangements  of  the  gastro-intestinal  tract,  or  rather 
perhaps  the  presence  in  the  intestinal  tract  of  some  substance  or 
substances,  which  prevent  the  absorption  of  the  iron  of  the  food,  or 
whic'i  split  up  the  soluble  iron  compounds  and  render  them  unfit 
for  absorption  into  the  blood,  may  perhaps  have  some  influence  in 
the  production  of  the  condition.  Constipation,  though  it  cannot  in 
my  opinion  be  regarded  as  the  essential  and  fundamental  cause 
of  the  disease,  probably  acts  as  a  contributory  cause,  in  some  cases 
at  all  events.  Again,  if  Stockman's  analyses  as  to  the  small  amount 
of  iron  in  the  food  of  chlorotic  patients  are  of  general  application, 
it  must  be  allowed  that  this  (the  deficiency  of  iron  in  the  food),  if 
it  is  present  at  the  onset  of  the  disease,  probably  plays  some 
part  in  the  production  of  the  disease,  though,  so  far  as  I  see,  there 
is  no  reason  to  suppose  that  it  is  the  chief  or  essential  cause. 


CHLOROSIS.  31 


Clinical  History. 


The  onset  of  the  disease  is  usually  insidious.  The  patient 
gradually  loses  colour,  complains  of  debility,  and  inability  for  exer- 
cise, becomes  short  of  breath,  and  suffers  from  palpitation  and 
giddiness — in  short,  the  disease  is  characterised  by  the  presence  of 
symptoms  which  are  associated  with  profound  anaemia  or  a  marked 
deficiency  of  haemoglobin  in  the  blood,  and  which  result  from  the 
irritable  and  enfeebled  condition  of  the  heart,  which  the  deficiency 
of  haemoglobin  and  the  consequent  imperfect  oxygenation  of  the 
heart  muscle  occasion. 

In  order  to  understand  the  clinical  features  of  chlorosis  and  to 
intelligently  and  successfully  treat  cases  of  chlorosis,  it  is  essential 
to  remember  that  the  fundamental  feature  of  the  disease  is  a  deficiency 
of  hcemoglobiu  in  the  blood.  And  since  the  function  of  the  haemo- 
globin is  to  carry  oxygen  to  the  tissues,  a  deficiency  in  haemoglobin 
means  a  deficient  supply  of  oxygen  to  the  tissues.  Now,  when  the 
supply  of  oxygen  to  the  tissues  is  deficient,  they  are  apt  to  undergo 
fatty  degeneration  ;  hence  in  cases  of  chlorosis  the  heart  muscle 
and  the  other  tissues  and  organs  of  the  body  are  apt  to  become 
fatty.  In  consequence  of  the  deficiency  of  haemoglobin  the  nutri- 
tion of  the  cardiac  muscle  becomes  impaired,  a  condition  of  irritable 
weakness  of  the  heart,  and,  if  the  chlorosis  is  severe  and  long  con- 
tinued, cardiac  dilatation  and  fatty  degeneration  are  developed. 
In  consequence  of  nutritive  disturbances  in  the  walls  of  the  stomach, 
dyspepsia,  dilatation,  and  it  may  be  ulceration  are  in  some  cases 
produced  ;  etc. 

The  exact  manner  in  which  chlorosis  leads  to  the  production  of  ulceration  of 
the  stomach  is  still  somewhat  uncertain.  One  view  is  that  the  anaemia  pro- 
duces lowered  vitality  in  the  gastric  mucous  membrane  ;  another  that  there  is 
hemorrhagic  extravasation  in  the  mucous  membrane  ;  a  third  that  embolic  or 
thrombotic  destruction  of  the  nutrient  vessels  causes  necrotic  softening  ;  and 
that  the  mucous  membrane  the  vitality  of  which  is  lowered  in  any  of  these  ways 
is  acted  on  and  eroded  (digested  so  to  speak)  by  the  gastric  juice. 

General  appearance.— Patients  who  are  affected  with  a  high 
degree  of  chlorosis  are,  as  a  rule,  well  covered  with  fat,  but  their 
muscles  are  usually  soft  and  flabby.  In  some  of  the  cases,  more 
especially  in  those  cases  in  which  dyspepsia  or  ulceration  of  the 
stomach  are  associated  with  the  anaemia,  there  is  more  or  less 
emaciation. 

In  many  cases,  the  mammae  are  full,  the  external  genitals  and 
the  pubic  hair  well  developed  ;  but  in  other  cases  the  reverse 
is  the  case,  the  mammae  and  genital  organs  being  imperfectly 
developed. 


32  DISEASES   OF  THE   BLOOD. 

The  skin  and  mucous  membranes  are  pale,  and  the  skin  often 
has  a  greenish-yellow  colour  ;  hence  the  term  "  green  sickness  " 
which  has  been  given  to  the  disease.  The  green  hue  is  usually 
more  marked  in  dark-complexioned  than  in  fair-complexioned 
girls.  In  blondes,  the  complexion  often  has  a  beautiful  rosy-red 
tint  when  the  patient  first  comes  under  the  notice  of  the  physician  ; 
patients  suffering  from  chlorosis  flush  readily  ;  their  skin  is  usually 
thin  and  delicate  ;  the  temporary  tinting  of  the  skin  which  results 
from  the  flushing  is  very  becoming,  for  many  of  the  girls  who  are 
affected  with  chlorosis  are  very  pretty.  After  the  temporary 
excitement  subsides,  the  face  becomes  pale ;  and  in  severe  cases 
both  the  lips  and  skin  may  look  almost  entirely  bloodless.  Pallor 
of  the  buccal  mucous  membrane  and  conjunctiva  is,  from  a  diag- 
nostic point  of  view,  of  more  importance  than  pallor  of  the  skin. 
In  some  cases  in  which  the  buccal  mucous  membrane  is  pale,  the 
palpebral  conjunctiva  is  injected  with  fine  vessels. 

Symptoms  and  complaints. — Patients  affected  with  chlorosis 
complain  of  weakness  and  debility,  inability  for  prolonged  and  sus- 
tained efforts  either  of  body  or  mind,  shortness  of  breath  on 
exertion,  palpitation,  giddiness  on  stooping  the  head  and  on 
suddenly  rising  from  the  recumbent  to  the  erect  position.  In 
advanced  stages  of  the  disease,  the  feet  and  lower  part  of  the  legs 
may  be  cedematous,  but  marked  dropsy  is  rare.  In  some  cases  the 
eyelids  are  somewhat  swollen  and  puffy-looking.  The  oedema  is 
probably  due  partly  to  the  watery  condition  of  the  blood,  and 
partly  to  the  enfeebled  condition  of  the  heart.  A  slight  degree  of 
exophthalmos  is  sometimes  present.  The  thyroid  gland  is  not 
un frequently  somewhat  enlarged.  I  do  not  of  course  refer  to  cases 
of  exophthalmic  goitre  which  are  complicated  with  chlorosis — a 
combination  of  diseases  which  is  not  uncommon. 

The  physiognomy  is  usually  so  characteristic  and  the  symptoms 
associated  with  the  anaemia  so  constant  that  in  well-marked  cases 
of  chlorosis  it  is  usually  possible  to  predict  most  of  the  symptoms 
from  which  the  patient  is  suffering  before  a  single  question  has 
been  asked. 

The  condition  of  the  blood. — This  is  of  the  greatest  import- 
ance. A  drop  of  blood  obtained  by  pricking  the  ear  or  finger 
is  thin,  pale  and  watery-looking.  In  many  cases,  the  puncture 
bleeds  more  freely  than  one  would  expect  considering  the  markedly 
bloodless  appearance  of  the  patient. 

In  slight  cases,  the  red  blood  corpuscles  are  little  if  at  all 
diminished  in  number.  In  more  severe  cases,  they  usually  number 
from   3,500,000  to  2,500,000  per  cubic  millimetre.      In  exceptional 


CHLOROSIS.  33 

cases  the  reduction  is  much  more  considerable.  Hayem  has 
reported  a  case  of  chlorosis  in  which  the  blood  corpuscles  num- 
bered only  1,300,000  ;  in  four  of  my  cases,  the  red  corpuscles 
numbered  1,800,000,  1,675,000,  1,600,000  and  1,425,000  per  cubic 
millimetre  respectively ;  but  such  a  marked  decrease  is  quite 
exceptional. 

In  77  cases  of  chlorosis,  observed  by  Cabot  ("  Clinical  Examina- 
tion of  the  Blood,"  p.  134),  the  red  corpuscles  averaged  4,050,000  per 
cubic  millimetre.  In  the  80  cases  which  I  have  included  in  Table 
2,  the  red  corpuscles  averaged  3,437,300  per  cubic  millimetre. 
With  few  exceptions  these  cases  were  all  in-patients,  and  as  only 
the  more  severe  cases  were  admitted  to  hospital,  and  as  many  of 
the  cases  included  in  the  table  were  also  suffering  from  dyspepsia, 
or  slight  ulceration  of  the  stomach,  they  may  be  regarded  as  aggra- 
vated and  severe  cases  of  the  disease.* 

The  essential  blood  change  is  a  diminution  in  the  haemoglobin. 
The  total  amount  of  haemoglobin  may  be  reduced  to  20  per  cent, 
or  even  lower.  In  the  80  cases  included  in  Table  2,  the  average 
amount  of  haemoglobin  as  estimated  by  Gowers'  instrument  equalled 
34  per  cent.  ;  but  since  Gowers'  instrument  reads  low,  the  average 
amount  of  haemoglobin  (calculated  on  the  basis  that  Gowers'  instru- 
ment reads  90  instead  of  100  per  cent.)  equalled  37.7  per  cent. 
In  four  of  my  cases,  the  percentage  of  haemoglobin  as  estimated 
by  Gowers'  instrument  equalled  16,  10,  15  and  19  per  cent- 
respectively. 

Now,  since  the  reduction  of  the  red  corpuscles  is  in  the  great 
majority  of  cases  proportionately  much  less  than  this,  the  individual 
richness  in  haemoglobin  of  the  red  corpuscles  is  considerably  below 
the  normal.  In  many  cases  the  individual  richness  of  the  red  blood 
corpuscles  in  haemoglobin  is  less  than  half  the  normal — for  example, 

H     _30 
R.C.         66  • 

In  the  80  cases  included  in  Table  2,  the  haemoglobin  averaged 
34  per  cent,  as  estimated  by  Gowers'  instrument;  and  the  individual 
corpuscular  richness  in  haemoglobin  equalled  44  per  cent. ;  or,  after 
correction  (taking  the  normal  amount  of  haemoglobin  as  estimated 
by  Gowers'  instrument  at  90  instead  of  100  per  cent.),  37.7  per  cent, 
and  49.4  per  cent,  respectively. 

In  the  77  cases  tabulated  by  Cabot,  the  haemoglobin  averaged 


*  In  none  of  the  cases  included  in  the  table  were  the  symptoms  of  ulceration 
of  the  stomach  prominent ;  in  all  cases  of  combined  chlorosis  and  ulceration  of 
the  stomach,  in  which  the  ulceration  of  the  stomach  was  the  prominent  con- 
dition, the  case  has  been  classified  under  the  head  of  ulcer  of  the  stomach. 

C 


34 


DISEASES   OF   THE   BLOOD. 


Table  2. — Chlorosis. 


Case-book. 

d 

s  . 

V, 

Age. 

Red 
Corpuscles. 

V 

a  oj 
_o  g 

Menstruation. 

Bowels. 

Remarks. 

No. 

Vol. 

Page 

"o  0 

I 

I 

27 

23 

2,920,000 

55 

.92 

Amenorrhoea. 

Constipated. 

Dyspepsia. 

2 

I 

I02 

22 

4,030,000 

50 

.61 

Constipated. 

Dyspepsia.     ?  Ulcer  of 
stomach.  Headache. 

3 

I 

130 

17 

3,610,000 

54 

■77 

Normal. 

Regular. 

Rheumatism. 

4 

3 

18 

17 

2,860,000 

32 

•55 

Amenorrhcea. 

Dyspepsia.     ?  Ulcer  of 
stomach.  Headache. 

5 

4 

114 

26 

3,560,000 

43 

.60 

Normal. 

Dyspepsia. 

6 

4 

IO8 

22 

3,S2O,O0O 

40 

•54 

Normal. 

Constipated. 

7 

6 

IOO 

18 

3,820,000 

43 

•58 

Constipated. 

Erythema  of  legs. 

S 

8 

71 

23 

4,l6o,000 

35 

.41 

Constipated. 

Slight  dyspepsia. 

9 

8 

54 

iS 

3,460,000 

32 

•45 

Normal. 

Constipated. 

Thin. 

10 

8 

117 

20 

3,800,000 

32 

.41 

Amenorrhoea. 

Regular. 

Headache.    Vomiting. 

11 

9 

120 

17 

4,050,000 

5o 

.61 

Constipated. 

Epigastric  pain.    Sick- 
ness.    Headache. 

12 

10 

5 

15 

1,600,000 

16 

.48 

Amenorrhoea. 

2  or  3  motions 
daily. 

Headache. 

13 

10 

16 

21 

1,675,000 

10 

•29 

Amenorrhoea. 

Constipated. 

14 

10 

24 

27 

3>337,ooo 

36 

•54 

R.     Scanty    and 
pale. 

Regular. 

Thirst.       Neuralgia. 
Headache.  Nervous 
vomiting. 

15 

10 

39 

25 

4,000,000 

48 

.60 

Normal. 

Regular. 

Epigastric  pain. 

16 

10 

47 

21 

3,220,000 

50 

•77 

Amenorrhcea. 

Constipated. 

Thirst.     Ulceration  of 
stomach. 

17 

10 

56 

18 

2,212,000 

15 

•32 

Constipated. 

Headache.    Backache. 

18 

10 

102 

31 

4,000,000 

60 

•75 

Normal. 

Constipated. 

Backache. 

19 

11 

58 

18 

3,860,000 

19 

.24 

Constipated. 

Infra- mammary   pain. 
Morning  sickness. 

20 

11 

92 

26 

3,750,000 

30 

•39 

Amenorrhcea. 

Severe  headache. 

21 

11 

96 

19 

3,725,000 

35 

.46 

Regular. 

22 

12 

87 

16 

1,425,000 

28 

.96 

Gastricpain.  Vomiting. 
Enlarged  thyroid. 

23 

12 

109 

l8 

3,750,000 

30 

•39 

R.   Scanty  &  pale. 

Constipated. 

24 

12 

150 

23 

2,500,000 

40 

.81 

R.  Dysmenorrhoea 
Leucorrhcea. 

Very  bad  teeth. 

25 

12 

158 

14 

3,000,000 

26 

.42 

Regular. 

Vomiting.       Swollen 
glands  in  neck. 

26 

13 

97 

18 

3,300,000 

30 

•45 

R.   Scanty&  pale. 

Regular. 

27 

15 

132 

18 

3,450,000 

40 

•58 

Normal. 

Regular. 

28 

16 

108 

19 

2,240,000 

25 

•55 

Regular. 

Mild    articular    rheu- 
matism. 

29 

20 

131 

19 

4,900,000 

58 

■59 

Enl'ged  glands  in  neck. 

30 

21 

9i 

19 

4,700,000 

50 

•52 

Amenorrhcea. 

Constipated. 

Great  thirst. 

3i 

22 

10 

21 

2,800,000 

24 

.41 

Irregular. 

Constipated. 

Thirst.     Headache. 

32 

22 

3i 

21 

3,000,000 

40 

.66 

Normal. 

Constipated. 

Dyspepsia. 

33 

22 

5i 

16 

3,850,000 

40 

•5i 

Amenorrhoea. 

Constipated. 

Sickness.    Infra-mam- 
mary pain. 

34 

22 

99 

17 

2,000,000 

38 

•95 

Amenorrhcea. 

Constipated. 

35 

22 

157 

18 

2,800,000 

20 

•35 

Amenorrhoea. 

Constipated. 

Dyspepsia.  Headache. 

36 

23 

34 

17 

3,100,000 

35 

•55 

Amenorrhcea. 

Constipated. 

37 

24 

37 

20 

3,400,000 

30 

.41 

Amenorrhoea  and 
Leucorrhcea. 

Constipated. 

Vomiting.      Frontal 
headache. 

38 

24 

43 

21 

2,900,000 

20 

•34 

Normal. 

Constipated. 

39 

24 

47 

25 

3,300,000 

26 

•38 

Constipated. 

40 

24 

98 

16 

3,500,000 

30 

.42 

Never    menstru- 
ated. 

Constipated. 

41 

24 

116 

19 

2,890,000 

40 

.68 

Amenorrhoea. 

Regular. 

42 

26 

1  l6 

21 

2,200,000 

22 

•50 

Irregular. 

Constipated. 

Headache.    Vomiting. 

4"? 

12 

1  10 

23 

•3.200,000 

^8 

1  .w 

Normal. 

Constipated. 

CHLOROSIS. 

35 

Case-book. 

d 

r,   . 

*0  T3 

Age. 

Red 

s  « 

:-.   u 

Menstruation. 

Bowels. 

Remarks. 

No. 

Corpuscles. 

-ol 

0    n 

Vol. 
35 

Page 
113 

■0  S 

44 

26 

3,520,000 

35 

•49 

Amenorrhoea. 

Constipated. 

45 

35 

131 

16 

4,100,000 

26 

•30 

Amenorrhoea. 

Constipated. 

Headache.    Vomiting. 

46 

36 

72 

21 

4,800,000 

65 

.64 

Irregular. 

Constipated. 

47 

36 

78 

29 

4,800,000 

40 

.41 

Amenorrhoea. 

.48 

36 

119 

18 

4,100,030 

35 

.41 

Amenorrhoea. 

Constipated. 

49 

37 

59 

22 

3,200  OOO 

25 

•38 

Amenorrhoea. 

5o 

38 

8 

i3i 

4,360,000 

40 

•45 

Never    menstru- 
ated. 

Constipated. 

51 

39 

32 

21 

4,320,000 

20 

.24 

Amenorrhoea. 

Regular. 

52 

39 

69 

17 

4,000,000 

40 

.50 

Amenorrhoea. 

Constipated. 

53 

40 

117 

17 

4,640,000 

3° 

•33 

Irregular. 

Constipated. 

Dyspepsia.  Headache. 

54 

41 

123 

18 

3,000,000 

3° 

.50 

Irregular. 

Constipated. 

Pain  in   chest.     Con- 
genital syphilis. 

55 

42 

124 

26 

4,230,000 

38 

•44 

R.  Scanty  &  pale. 

Constipated. 

Crampsin  legsatnight. 

56 

45 

133 

19 

2,8§0,000 

29 

.50 

Normal. 

Constipated. 

57 

47 

104 

18 

2,840,000 

24 

.41 

R.    Scanty    and 
pale. 

Constipated. 

5§ 

48 

52 

20 

4,860,000 

28 

.20 

Amenorrhoea. 

Constipated. 

Occasional  vomiting. 

59 

49 

25 

24 

3,500,000 

45 

.64 

Irregular. 

Constipated. 

Vomiting.    Headache. 

60 

49 

68 

26 

4,700,000 

52 

•54 

61 

5o 

81 

20 

2,300,000 

30 

.64 

Slight     menor- 
rhagia. 

Regular. 

Slight  mitral  stenosis. 

62 

5o 

64 

17 

3,500,000 

30 

.42 

Sickness. 

63 

50 

114 

25 

2,430,000 

26 

•5i 

Amenorrhoea. 

Constipated. 

Dyspepsia. 

64 

5i 

20 

18 

3,8oO,O0O 

35 

•45 

R.   Scanty&  pale. 

Constipated. 

Thirst. 

65 

53 

95 

24 

5,200,000 

48 

.46 

Irregular. 

Constipated. 

Dyspepsia. 

66 

53 

131 

23 

3,500,000 

40 

•58 

Irregular. 

Constipated. 

Epigastric  pain. 

67 

54 

125 

22 

2,800,000 

35 

.61 

Amenorrhoea. 

Constipated. 

68 

55 

68 

21 

1,800,000 

20 

•55 

Irregular.      Leu- 
corrhcea. 

Dyspepsia. 

69 

55 

74 

21 

3,300,000 

35 

•52 

Amenorrhoea. 

Constipated. 

Headache.    Backache. 

70 

55 

127 

24 

4,480,000 

35 

.38 

Amenorrhoea. 

Constipated. 

Pains  in  arms  and  legs. 

7i 

56  |  56 

17 

3,200,000 

30 

.46 

Amenorrhoea. 

Constipated. 

Dyspepsia.  Headache. 

72 

57    106 

29 

3,600,000 

35 

•47 

73 

10 

i  77 

19 

3,500,000 

40 

•57 

74 

13 

117 

17 

3,40O,OOO 

3° 

•  44 

75 

13 

ji93 

19 

3,590,000 

35 

.48 

Amenorrhoea. 

76 

36 

;i59 

20 

3,500,000 

25 

•35 

Amenorrhoea. 

77 

40 

63 

19 

3,200,000 

26 

•39 

78 

40 

ll51 

12 

3,100,000 

25 

•39 

79 

49 

217 

17 

3,l6o,000 

24 

•37 

Constipated. 

80 

1  53 

|i67 

19 

2,100,000 

20 

•45 

R.   Scanty&pale 

Constipated. 

1 

\vera 

ge  = 

20 

3,437,300 

34 

•  49 

Note. — The  colour  index  or  the  haemoglobin  richness  of  each  individual  red  blood  corpuscle  is 
arrived  at  by  dividing  the  percentage  of  haemoglobin  by  the  percentage  of  red  corpuscles.  Thus  the 
average  number  of  red  corpuscles  in  the  80  cases  of  chlorosis  included  in  the  table  was  3,437>3°° 
per  cubic  millimetre  ;  and  taking  the  average  number  of  red  corpuscles  per  cubic  millimetre  in  the 
female  at  4,500,000,  the  average  percentage  of  red  corpuscles  in  the  80  cases  included  in  the  table 
was  76  per  cent.  The  actual  average  percentage  of  haemoglobin  in  the  80  cases  included  in  the  table 
(as  estimated  by  Gowers'  instrument)  was  34.  But  Gowers'  instrument  reads  low  (85  to  90  instead 
of  100  per  cent.).  Therefore,  taking  the  reading  of  Gowers'  instrument  at  90  instead  of  100  per 
■cent.,  the  average  percentage  of  haemoglobin  in  the  80  cases  of  chlorosis  included  in  the  table  should 
be  37  per  cent.     The  colour  index  would  therefore  be  :  — 

Average  percentage  of  haemoglobin  37.7 

Average  percentage  of  red  corpuscles        76.3 
Strictly  speaking,  the  normal  percentage  of  haemoglobin  in  the  female  should  be  represented  as 
less  than  90  %  (as  estimated  by  Gowers'  instrument),  and  consequently  the  colour  index  should  be 
higher  than  .49  ;  for  the  amount  of  haemoglobin  in  the  blood  of  the  female  is  probably,  on  the 
-average,  8  °/0  or  10  °/0  less  than  in  the  blood  of  the  male — which  is  usually  taken  as  the  standard. 


=  .49. 


36  DISEASES   OF   THE   BLOOD. 

41  per  cent.;  and  the  individual  corpuscular  richness  in  haemoglobin 
(the  colour  index,  as  he  terms  it)  equalled  50  per  cent. 

In  chlorosis,  the  blood  corpuscles  are  markedly  paler  than 
normal ;  many  of  the  red  corpuscles  are  somewhat  smaller  than 
normal,  but  in  most  of  the  cases  which  I  have  carefully  observed,, 
the  alterations  in  size  and  shape  have  not  been  marked  ;  in  the 
advanced  stages  of  aggravated  cases  unusually  large  red  corpuscles 
(megalocytes)  are  occasionally  present,  but  very  small  red  corpuscles 
(the  smallest  sized  microcytes)  are  in  my  experience  very  rare.  In 
those  cases  of  profound  chlorosis  in  which  the  red  blood  corpuscles 
are  greatly  reduced  in  number  (but  this,  it  must  be  remembered,  is 
quite  exceptional),  and  in  which  this  marked  reduction  is  of  long 
duration,  in  other  words,  in  those  rare  cases  of  chlorosis  in  which  an 
excessive  production  of  red  blood  corpuscles  is  demanded  for  a 
length  of  time,  one  would  naturally  expect  that  the  red  blood  cells 
would  be  imperfectly  formed  and  consequently  altered  in  size  and 
shape.  As  a  matter  of  fact,  the  extreme  alterations  in  size  and 
shape  of  the  red  blood  corpuscles,  which  are  so  characteristic  of 
pernicious  anaemia,  have  rarely  been  present  even  in  the  most 
severe  cases  of  chlorosis  which  have  come  under  my  own  notice. 
I  have,  however,  noticed  a  considerable  degree  of  poikilocytosis  in 
some  cases. 

With  regard  to  the  alterations  in  size  and  shape  of  the  red 
corpuscles,  Cabot  states  (p.  136):  "Deformities  in  size  and  shape  are 
very  common  in  all  advanced  cases,  but  often  absent  in  mild  or 
moderate  ones.  They  present  no  special  peculiarities  except 
that  macrocytes  are  relatively  rare  and  microcytes  relatively 
common.  In  the  severest  cases,  however,  the  macrocytes  begin 
to  get  more  numerous  and  we  approach  the  picture  of  pernicious 
anaemia." 

In  chlorosis,  the  large  white  blood  corpuscles  are  usually  less, 
numerous  than  in  health;  the  small  white  corpuscles  (lymphocytes) 
may  be  more  numerous  than  normal. 

The  blood-plates  are  usually  increased  in  number,  and  Max 
Schultze's  granular  masses  are  often  numerous  and  prominent. 

The  blood  usually  coagulates  rapidly  and  the  fibrin  network  is 
well  marked. 

Nucleated  red  blood  corpuscles  and  myelocytes  are,  it  is  said, 
occasionally  present  in  the  blood  ;  Dr  Muir  informs  me  that  in  his 
experience  this  only  occurs  in  very  extreme  cases. 

In  some  cases  I  have  seen  appearances  which  seemed  to  be 
suggestive  of  the  presence  of  micro-organisms  ;  but  in  all  of  the 
cases  of  chlorosis  in  which  I  have  inoculated  sterilised  gelatine  with 


CHLOROSIS.  37 

the  blood — and  I  have  from  time  to  time  made  quite  a  number  of 
observations  of  this  kind — the  results  have  been  negative. 

Lloyd  Jones  states  that  the  specific  gravity  of  the  blood  in 
chlorosis  is  always  considerably  diminished  (from  1 050-1060,  the 
normal,  to  1030- 1045).  He  further  concludes  that  since  his  obser- 
vations show  that  the  specific  gravity  of  the  serum  obtained  from 
chlorotic  blood,  as  a  rule,  differs  little  if  at  all  from  the  serum  of 
the  healthy  (while  it  may  be  increased  or  more  rarely  diminished), 
the  marked  diminution  of  the  specific  gravity  of  the  whole  blood 
in  chlorosis  must  be  largely  either  due  to  an  absolute  diminution 
of  the  number  of  red  corpuscles,  or  an  absolute  increase  in  the 
amount  of  plasma.* 

The  following  notes  descriptive  of  the  condition  of  the  blood  in 
three  well-marked  cases  of  chlorosis  may  be  taken  as  fairly  typical 
and  illustrative  : — 

Case  I  (No.  35  in  Table  2). — Female,  aged  18  :  profound  and 
typical  chlorosis. 

The  condition  of  the  blood  on  19th  December,  1894,  was  as 
follows  : — Red  corpuscles,  2,800,000  ;  haemoglobin  =  20  per  cent.  ; 
colour  index,  .35  ;  slight  excess  of  white  corpuscles,  both  small  and 
large  ;  blood-plates  numerous  and  Max  Schultze's  granular  masses 
in  excess ;  a  strong  tendency  to  fine  fibrin-felt  formation. 

The  red  corpuscles  for  the  most  part  go  into  rouleaux ;  they  are 
pale,  the  majority  of  them  of  normal  size  or  perhaps  slightly  smaller 
than  normal ;  a  few  larger  and  a  few  distinctly  smaller  than  normal, 
but  no  very  large  corpuscles  and  no  small  microcytes.  A  few  of 
the  red  corpuscles  appeared  to  be  nucleated  in  consequence  of  the 
concentration  of  the  haemoglobin  in  one  part  of  the  corpuscle.  A 
few  of  the  red  corpuscles  are  mis-shaped,  tailed  and  biscuit-shaped 
(a  moderate  degree  of  poikilocytosis).  Some  small,  pale,  apparently 
actively-moving,  minute  masses  of  protoplasm  (?  organisms)  ;  some 
of  them  are  rod-shaped,  one  distinctly  swollen  at  each  end. 

Case  2  (No.  39  in  Table  2). — Female,  aged  25:  typical  chlorosis. 

The  condition  of  the  blood  was  as  follows  : — Red  corpuscles, 
3,300,000  ;  haemoglobin  =  26  per  cent. ;  colour  index,  .38.  The  red 
corpuscles  go  into  rouleaux  ;  they  are  pale  ;  no  poikilocytosis  ;  a 
few  microcytes ;  no  megalocytes  ;  no  apparently  or  actually 
nucleated  red  corpuscles.  There  is  no  excess  of  white  corpuscles  ; 
those  which  are  present  are  mostly  of  large  size  and  coarsely 
granular.  The  blood-plates  and  Max  Schultze's  granular  masses 
are  in  some  excess. 

Case  3  (No.  40  in  Table  2). — Female,  aged  16:  typical  chlorosis. 
*  "  Chlorosis,"  by  Dr  E.  Lloyd  Jones,  p.  23. 


3  8  DISEASES   OF   THE    BLOOD. 

The  condition  of  the  blood  was  as  follows  :  Red  corpuscles,. 
3,500,000 ;  haemoglobin  =  30  per  cent.  ;  colour  index,  .42.  The 
rouleaux  formation  is  somewhat  imperfect  ;  the  red  corpuscles  are 
pale  ;  a  moderate  degree  of  poikilocytosis  ;  a  few  microcytes  ;  no 
megalocytes.  Leucocytes  less  numerous  than  normal.  Blood- 
plates  and  Max  Schultze's  granular  masses  about  normal  in  number. 

Cabot  sums  up  the  characters  of  the  blood  in  chlorosis  as 
follows  : — 

"  1.  Blood  as  a  whole:  Very  pale  in  marked  cases,  very  fluid, 
but  coagulates  rapidly.  Fibrin  not  increased.  Specific  gravity 
usually  low,  running  parallel  with  the  haemoglobin. 

2.  Red  cells  :  Average  4,000,000  when  patient  is  first  seen,  very 
rarely  go  below  1, 000,000.  The  majority  of  them  are  small-sized, 
pale,  often  deformed.  Nucleated  corpuscles  are  rare  (normoblasts 
as  a  rule). 

3.  White  cells,  not  increased. 
Lymphocytosis  ;  occasionally  eosinophilia. 

4.  Blood-plates  increased."  * 

The  condition  of  the  heart  and  pulse  in  cases  of  chlorosis- 
is  very  important.  As  I  have  already  stated,  palpitation  is  a 
frequent  symptom  ;  it  is  due  to  the  irritable  weakness  of  the  heart 
muscle.  Slight  excitements  whether  of  body  or  mind  produce  an 
unusual  effect  upon  the  irritable  heart.  The  pulse  is  readily  excited. 
In  the  earlier  stages  of  the  disease,  the  pulse  tension  is  usually  good, 
in  fact  it  may  be  higher  than  normal  ;  but  when  the  chlorosis  is 
long-continued  or  severe,  the  pulse  tension  has,  in  my  experience,, 
been  invariably  low.  Sphygmographic  tracings  often  show  the 
undue  irritability  of  the  heart  in  a  striking  way. 

When  the  patient  is  perfectly  tranquil  and  at  rest  the  cardiac 
impulse  is  usually  feeble  and  diffuse ;  under  excitement,  the  apex 
beat  becomes  much  more  forcible  and  well  defined  ;  the  apex  beat 
is  usually  displaced  somewhat  downwards  and  outwards  to  the  left; 
epigastric  pulsation  is  often  present.  The  area  of  cardiac  dulness 
is  usually  increased  both  to  the  right  and  to  the  left.  The  ventricles, 
particularly  the  left  ventricle,  are  usually  more  or  less  dilated.  On 
auscultation,  a  systolic  murmur  is  usually  present  in  the  pulmonary 
and  often  in  the  mitral  and  tricuspid  areas.  Less  frequently  a 
systolic  murmur  is  also  audible  in  the  aortic  area.  The  mitral  and 
tricuspid  murmurs  are  doubtless  due  to  regurgitation,  apparently 
the  result  of  muscular  and  relative  incompetence. 

*  "Clinical  Examination  of  the  Blood,"  p.  139. 


CHLOROSIS.  39 

The  exact  mode  of  production  of  the  pulmonary  murmur  is  more 
difficult  to  explain.  In  my  opinion  the  balance  of  evidence  seems 
to  show  that  it  is  due  partly  to  the  altered  condition  of  the  blood, 
partly  to  the  altered  relationship  of  the  pulmonary  orifice  to  the 
pulmonary  artery,  and  partly  to  the  altered  mode  of  contraction  of 
the  heart.  In  cases  of  chlorosis  the  pulmonary  artery  is  usually 
somewhat  dilated  and  the  action  of  the  heart  is,  at  all  events  under 
excitement,  quick  and  the  contraction  of  the  cardiac  muscle  more 
rapid  and  sudden  than  in  health.  The  sudden  propulsion  of  a 
wave  of  hydraemic  blood  into  the  pulmonary  artery  which  is,  in 
comparison  to  the  orifice,  relatively  dilated,  seems  to  me  the  most 
reasonable  explanation  of  the  mode  of  production  of  the  pulmonary 
murmur. 

I  am  quite  unable  to  accept  Dr  George  Balfour's  theory  that  the 
murmur  is  a  systolic  mitral  murmur  propagated  to  the  pulmonary 
area  through  the  appendix  of  the  left  auricle,  which  he  states  comes 
to  the  surface  and  overlaps  the  pulmonary  artery  in  the  2nd  left 
interspace.  I  need  not  discuss  the  question  in  detail,  for  I  have 
considered  it  at  great  length  in  my  work  on  the  heart.  I  need  only 
repeat  that  Dr  Balfour's  theory  seems  contradicted  by  the  following 
facts: — (1)  That  in  some  of  the  cases  of  chlorosis  in  which  the 
systolic  murmur  in  the  pulmonary  area  is  well  marked,  there  is  no 
mitral  murmur,  i.e.,  no  murmur  can  be  heard  in  the  mitral  area ; 
(2)  That  in  cases  of  profound  anaemia  which  prove  fatal  (cases  of 
pernicious  anaemia,  for  example,  in  which  the  same  pulmonary 
murmur  is  present),  the  appendix  of  the  left  auricle,  as  Dr  William 
Russell  was  the  first  to  point  out  and  as  my  pathological  experience 
abundantly  confirms,  rarely  if  ever  overlaps  the  pulmonary  artery  ; 
owing  to  the  dilatation  of  the  right  heart  and  the  twisting  of  the 
organ  on  itself  which  results  therefrom,  the  left  auricular  appendix 
is  usually  entirely  concealed  by  the  pulmonary  artery  and  does  not 
come  to  the  surface  of  the  chest  at  all ;  (3)  The  aortic  systolic  mur- 
mur is  clearly  not  the  result  of  mitral  regurgitation,  but  in  some 
cases  at  all  events  appears  to  be  produced  at  the  aortic  orifice  (in 
other  cases  it  is  perhaps  the  pulmonary  systolic  murmur  heard  in 
the  aortic  area).  Now,  if  a  systolic  murmur  can  in  cases  of  chlorosis 
be  produced  at  the  aortic  orifice,  there  is  every  reason  to  suppose 
that  it  may  also  be  produced  at  the  pulmonary  orifice  ;  (4)  That 
the  point  of  maximum  intensity  of  the  pulmonary  systolic  murmur 
in  cases  of  anaemia  and  chlorosis  is  not  situated  as  Balfour  states  at 
a  point  an  inch  and  a  half  or  more  outside  the  sternum,  but  at  the 
inner  end  of  the  2nd  left  interspace,  just  outside  the  sternum,  i.e., 
over  the  position  of  the  pulmonary  artery. 


40  DISEASES   OF   THE   BLOOD. 

Many  other  theories  have  been  advanced  to  account  for  the 
pulmonary  murmur  of  anaemia  ;  for  example,  Potain  is  of  opinion 
that  the  murmur  is  exocardial  and  produced  in  the  borders  of  the 
lung  which  surround  the  heart  ;  *  William  Russell  supposes  that  it 
is  due  to  the  stretching  and  compression  of  the  pulmonary  artery 
during  its  systolic  filling  by  the  distended  left  auricle ;  j"  Sansom 
thinks  that  the  cause  of  the  murmur  is  a  fibrillary  tremor  initiated 
at  the  overstrained  portion  of  the  right  ventricle,  the  conus  just 
below  the  valves,  and  perhaps  communicated  to  the  valves  them- 
selves so  that  they  vibrate  in  the  blood  current ;  J  and  Kingston 
Fowler  believes  that  it  is  due  to  the  altered  condition  of  the  blood 
and  the  relatively  dilated  condition  of  the  pulmonary  artery  to  the 
blood  in  anaemia.  Dr  Fowler's  explanation  seems  to  me  important; 
his  statement  on  the  point  is  as  follows  :§ — 

"  The  theory  which  to  my  mind  most  satisfactorily  explains  the 
mode  of  production  of  this  murmur,  and  also  that  heard  in  the 
veins  of  the  neck,  is  the  one  first  advocated  by  Chauveau,  ||  and 
may  be  stated  thus  : — '  In  anaemia  there  is  a  general  reduction  in 
the  volume  of  the  blood ;  the  blood-vessels  generally  with  two 
exceptions  adapt  their  diameter  to  the  reduced  volume.  The 
exceptions  are  (i)  the  aorta  and  pulmonary  artery,  which,  owing 
to  the  absence  of  the  contractile  and  the  preponderance  of  the 
elastic  element  in  their  walls,  cannot  reduce  their  diameter  pro- 
portionately to  that  of  the  current  passing  through  them  ;  (2)  the 
roots  of  the  innominate  veins  are  fixed  and  kept  permanently 
dilated  by  the  cervical  fascia,  which  not  only  ensheaths  them  but 
is  connected  with  the  sternum,  clavicle,  and  first  rib.  Hence,  whilst 
the  jugular  and  subclavian  veins  above  accommodate  themselves  to 
the  reduced  diameter  of  their  respective  currents,  the  commencing 
portion  of  the  innominate  vein  is  incapable  of  a  reduction  of  calibre 
and  becomes  relatively  dilated.'  The  blood-stream,  therefore,  at 
these  points  passes  through  a  narrow  orifice  into  a  portion  of  the 
vessel  having  a  wider  calibre,  which,  as  we  have  seen,  is  one  of  the 
conditions  necessary  for  the  production  of  a  murmur.  There  is 
an  interesting  confirmation  of  the  truth  of  this  theory  in  the  fact 

*  An  important  abstract  and  criticism  of  Potain's  views  are  given  by  Dr 
Gordon  Sanders  in  the  "Edinburgh  Medical  Journal,"  1897,  Vol.  i.,  p.  522. 

+  "  Investigation  into  Some  Morbid  Cardiac  Conditions,"  by  Dr  William 
Russell,  p.  53. 

I  "The  Diagnosis  of  Diseases  of  the  Heart  and  Aorta,"  by  Dr  A.  E.  Sansom, 
p.  285. 

>5  "On  the  Origin  of  Ana?mic  Murmurs,"  by  Dr  J.  K.  Fowler,  p.  28. 

||  "Gaz.  med.  de  Paris,"  1855. 


CHLOROSIS.  41 

that  a  similar  bruit  to  that  audible  in  the  innominate  veins  may 
occasionally  be  heard  over  the  cerebral  sinuses  at  the  torcular 
Herophili  where  the  same  conditions  as  to  non-contractility  are 
present,  and  also  in  the  fact  which  I  have  observed,  that  in  anaemic 
subjects  who  suffer  from  deafness  not  dependent  on  disease  of  the 
auditory  nerve  and  in  whom  the  conduction  of  the  skull  vibrations 
is  normal,  a  similar  sound  becomes  audible  on  the  affected  side. 
This  is,  no  doubt,  the  bruit  produced  in  the  lateral  sinus  conveyed 
to  the  ear  through  the  medium  of  the  temporal  bone." 

Some  authorities  state  that  a  diastolic  aortic  murmur  is  occa- 
sionally also  present;  but  the  correctness  of  this  opinion  is  doubtful. 
Dr  Sansom  has  suggested  that  what  appears  to  be  the  diastolic 
portion  of  a  double  aortic  murmur  is  probably  the  venous  murmur 
in  the  neck  heard  at  the  aortic  orifice  during  the  diastole  of  the 
heart. 

In  the  great  majority  of  cases  a  venous  hum  {bruit  de  diable) 
can  be  heard,  and  in  some  cases  very  distinctly  felt  by  the  finger, 
at  the  root  of  the  neck.  Occasionally,  more  especially  in  children 
affected  with  chlorosis,  a  loud  blowing  murmur  is  audible  over  the 
torcular  Herophili. 

In  many  cases  of  profound  chlorosis  the  veins  of  the  neck  are 
dilated.  A  flickering  pulsation  can  not  unfrequently  be  observed 
in  the  dilated  external  jugular  vein  on  careful  observation.  In  those 
cases  in  which  a  considerable  degree  of  tricuspid  regurgitation  is 
present,  true  venous  pulsation  in  the  external  jugulars  may  be  well 
marked. 

Venous  thromboses  occasionally  occur.  In  my  experience,  they 
are  much  more  frequent  than  some  writers  have  stated.  The  veins 
of  the  calf  are  usually  affected.  The  clot  not  unfrequently  extends 
up  to  the  femoral  vein.  The  onset  is  usually  rapid.  The  patient 
complains  of  pain  in  the  calf,  which  becomes  considerably  swollen, 
hard  and  exceedingly  tender  ;  the  foot  and  ankle  swell  ;  there  is 
often  at  the  same  time  a  marked  elevation  of  temperature.  In  rare 
cases,  the  condition  is  bilateral,  one  vein  being  first  affected  and  the 
corresponding  vein  on  the  opposite  side  after  an  interval  of  time 
becoming  involved.  In  very  rare  cases,  the  venous  sinuses  within 
the  cranium  may  become  thrombosed,  or  a  portion  of  clot  which  has 
been  detached  from  the  femoral  veins  may  be  swept  through  the 
circulation  and  may  produce  fatal  plugging  of  the  pulmonary 
artery.     No  cases  of  this  kind  have  come  under  my  own  observation. 

The  condition  of  the  alimentary  system. — Dyspeptic  de- 
rangements are  very  common  ;  there  is  usually  loss  of  appetite  ; 
not  unfrequently  the  appetite  is  capricious.     In  some  cases  there 


42 


DISEASES   OF   THE   BLOOD. 


is  flatulent  dyspepsia  with  pain  some  time  after  eating  ;  in  these 
cases  the  dyspepsia  is  probably  the  result  of  the  nutritive  altera- 
tions in  the  stomach  and  intestine  which  the  anaemic  condition  pro- 
duces, and  of  the  impairment  of  the  digestive  power  which  results 
therefrom.  In  a  considerable  proportion  of  cases  the  stomach  seems 
to  be  dilated.  In  other  cases,  ulceration  of  the  stomach  is  present. 
Chlorosis  and  simple  perforating  ulcer  of  the  stomach  are  often  met 
with  in  combination.  I  do  not  of  course  mean  to  say  that  most 
chlorotics  are  the  subjects  of  ulceration  of  the  stomach,  but  I  do  say 
that  in  a  large  proportion  of  cases  of  simple  (perforating)  ulcer 
of  the  stomach  the  patients  are  chlorotic.  The  anaemic  condition 
undoubtedly  predisposes  to  the  production  of  ulceration,  perhaps 
by  producing  a  debilitated  condition  of  the  gastric  mucous  mem- 
brane, structural  changes  in  the  gastric  mucous  membrane  (fatty, 
haemorrhagic,  etc.),  or  by  leading  to  the  formation  of  embolic  or 
thrombotic  plugging  of  the  nutrient  vessels. 

In  many  cases  of  chlorosis,  the  tongue  is  pale,  flabby,  indented 
by  the  teeth  and  slightly  furred  ;  in  others,  it  is  pale  and  clean. 

Constipation  is  usually  present,  but,  as  I  have  already  pointed 
out,  it  is  not  an  essential  or  invariable  symptom  ;  in  many  of  the 
cases  which  have  come  under  my  own  notice  the  bowels  have  been 
quite  regular.  In  the  80  cases  contained  in  Table  2,  in  49  the 
bowels  were  constipated;  in  13  there  was  no  constipation  (in  one 
of  these  cases  there  was  diarrhoea)  ;  and  in  18  cases  the  condition 
of  the  bowels  is  not  specially  mentioned  in  the  notes. 

In  many  cases,  the  teeth  are  carious. 

The  condition  of  the  uterine  and  ovarian  functions. — There 
is  usually  some  utero-ovarian  derangement,  generally  amenorrhcea. 
This,  as  I  have  already  stated,  is  a  result  and  not  a  cause  of  the 
disease.  As  I  have  already  pointed  out,  in  a  not  inconsiderable 
proportion  of  cases  of  chlorosis  the  menstruation  is  perfectly  regular 
in  time,  though  in  most  cases  of  this  kind  it  is  too  pale  and  scanty ; 
in  some  cases  the  menstruation  is  perfectly  natural  in  every  respect  ; 
in  other  cases  (but  they  are  rare)  there  is  menorrhagia.  In  the  80 
cases  analysed  in  Table  2,  in  29  cases  there  was  amenorrhcea  ;  in 
9  cases  the  menstruation  was  irregular  ;  in  7  cases  the  menstrua- 
tion was  regular  in  time  but  scanty  and  pale  ;  in  2  cases  the 
patients  had  never  menstruated  ;  in  1  case  there  was  slight  menor- 
rhagia ;  in  1  case  there  was  dysmenorrhcea  ;  in  1 1  cases  the  men- 
struation was  perfectly  normal  ;  and  in  20  cases  the  condition  of 
menstruation  is  not  specially  mentioned  in  the  notes. 

In  some  cases  of  chlorosis  there  is  leucorrhcea,  doubtless  the 
result  of  the  enfeebled  tone,  both  general  and  local  ;  in  3  of  the  80 


CHLOROSIS.  43 

cases  analysed  in  Table  2,  there  was  leucorrhoea.  Dysmenorrhcea 
is  occasionally  present,  but  it  is  very  doubtful  whether  it  is  the 
result  of  the  disease ;  I  am  strongly  disposed  to  think  that  its 
occasional  occurrence  is  purely  accidental. 

The  condition  of  the  nervous  system. — Nervous  symptoms, 
such  as  giddiness,  which  is  of  course  due  to  defective  blood  supply 
to  the  brain,  tinnitus,  headache,  a  feeling  of  weight  on  the  top  of 
the  head  and  of  tightness  round  the  head,  and  neuralgia  are  often 
complained  of.  The  late  Dr  Anstie  used  to  say  that  neuralgia  was 
a  prayer  on  the  part  of  the  nerves  for  a  better  supply  of  blood. 
Pain  in  the  region  of  the  heart  and  under  the  left  breast  (infra- 
mammary  myalgia  or  neuralgia)  is  a  common  symptom.  In  many 
cases  the  temper  is  irritable  and  uncertain.  Hysterical  symptoms 
are  of  frequent  occurrence.  Sleeplessness  is  comparatively  common. 
Fainting  may  occur  after  slight  effort,  such  for  example  as  suddenly 
rising  from  the  recumbent  to  the  erect  position,  after  a  watery 
evacuation  of  the  bowels,  etc.     A  nervous  cough  is  not  uncommon. 

The  condition  of  the  fundus  oculi  and  optic  discs. — In  a 
small  proportion  of  cases  of  chlorosis,  optic  neuritis  (papillitis) 
occurs.  It  is  especially  apt  to  be  developed  in  those  cases  in  which 
there  is  hypermetropia  ;  and  since  patients  affected  with  chlorosis 
frequently  suffer  from  headache,  the  combination  of  headache  with 
double  optic  neuritis  may  lead  the  physician  to  suppose  that  he  has 
to  deal  with  the  presence  of  a  cerebral  tumour. 

The  condition  of  the  urine. — There  is  rarely  any  characteristic 
change.  In  my  experience  the  urine  is  generally  normal  in  colour 
or  paler  than  normal,  and  of  low  specific  gravity,  but  free  from  any 
abnormal  constituents. 

The  temperature. — Intercurrent  attacks  of  fever  occasionally 
occur.  A  slight  degree  of  pyrexia  may  be  the  result  of  some 
agitation  or  excitement ;  a  decided  degree  of  pyrexia  is  usually  due 
to  the  development  of  venous  thrombosis  or  some  other  accidental 
complication.  Anaemic  fever  properly  so-called,  such  as  is  frequently 
seen  in  cases  of  pernicious  anaemia,  is  exceedingly  rare,  indeed  it  is 
doubtful  if  it  actually  occurs. 

Haemorrhages.  —  Epistaxis  occasionally  occurs,  but  other 
haemorrhages  are  exceedingly  rare,  except  in  those  cases  in  which 
haematemesis  results  from  associated  ulceration  of  the  stomach  ;  in 
cases  of  this  kind,  the  haemorrhage  is,  as  I  have  already  pointed  out, 
an  indirect,  not  a  direct,  'result  of  the  disease,  or  an  accidental 
and  associated  condition.  When  the  haematemesis  is  profuse  it 
may  of  course  materially  aggravate  the  anaemic  condition.  In  rare 
cases,  as  has  just  been  mentioned,  there  is  menorrhagia. 


44  diseases  of  the  blood. 

Diagnosis  and  Differential  Diagnosis. 

The  diagnosis  of  chlorosis  rarely  presents  any  difficulty.  In 
well-marked  cases  the  anaemia  is  self-obvious  and  the  symptoms 
highly  characteristic  ;  while  the  history  of  the  case  and  the  absence 
of  any  obvious  cause  for  the  bloodlessness,  such  as  severe  haemor- 
rhage, show  that  the  anaemia  is  a  primary  anaemia. 

The  chief  difficulty  occurs  in  those  cases  in  which  ulceration  of 
the  stomach  is  associated  with  the  chlorosis  and  in  which  there  has 
been  profuse  haematemesis.  As  has  been  already  stated,  the  two 
conditions  are  often  met  with  in  combination. 

The  Differential  Diagnosis  of  Chlorosis  and  of  Dyspepsia 
and  Ulceration  of  the  Stomach. — In  cases  in  which  dyspeptic 
symptoms  are  associated  with  chlorosis,  the  stomach  symptoms  may, 
as  I  have  already  stated,  be  the  result  either  of  anaemic  changes  with 
loss  of  functional  activity  in  the  walls  of  the  stomach,  or  of  ulceration. 
In  those  cases  in  which  haematemesis  occurs  and  in  which  the  patient 
comes  under  observation  for  the  first  time  after  the  occurrence  of 
the  bleeding,  it  is  important  to  determine  whether  the  patient  was 
bloodless  before  the  haematemesis,  or  whether  the  anaemia  is  the 
result  of  the  bleeding.  There  is  usually  no  difficulty  in  deciding 
this  point  by  a  careful  investigation  of  the  previous  history  of  the 
case. 

The  Differential  Diagnosis  of  Chlorosis  and  Phthisis. — In 
some  cases  of  phthisis,  there  is  a  considerable  degree  of  anaemia  at 
the  onset  of  the  disease  ;  but  these  cases  are  not  likely  to  be  mistaken 
for  chlorosis  by  a  careful  and  competent  observer.  The  diagnosis 
must  of  course  be  chiefly  based  upon  the  presence  of  physical  signs 
indicative  of  lung  disease,  and  the  examination  of  the  sputum  ;  but 
the  associated  symptoms  (more  especially  loss  of  weight,  pyrexia 
and  a  tendency  to  night  sweats)  are  also  of  importance. 

The  Differential  Diagnosis  of  Chlorosis  and  of  Bright's 
disease. — Bright's  disease  may  also  be  mistaken  for  chlorosis  by  a 
careless  observer.  The  condition  of  the  urine  at  once  shows  the 
true  nature  of  the  case. 

The  Differential  Diagnosis  of  Chlorosis  and  of  Lead  poisoning. 
—  In  some  cases  of  lead  poisoning  a  profound  degree  of  anaemia  is 
present,  and  if,  as  is  often  the  case,  the  patient  should  happen  to  be 
a  young  woman,  the  case  may  easily  be  mistaken  for  chlorosis.  In 
both  conditions,  constipation  and  amenorrhcea  are  usually  present. 
The  presence  of  a  blue  line  on  the  gums,  the  fact  that  the  patient 
has  been  exposed  to  lead  poisoning,  the  occupation  of  the  patient 
and  the  presence  of  other  symptoms  suggestive  of  plumbism  (such 


CHLOROSIS.  45 

as  dry  colic,  rheumatism,  wrist-drop,  etc.)  are  usually  sufficiently 
distinctive  of  the  true  nature  of  the  condition.  It  must,  however, 
be  remembered  that  the  two  conditions  may  occur  in  combination, 
i.e.,  lead  poisoning  may  be  developed  in  a  patient  already  affected 
with  chlorosis. 

The  Differential  Diagnosis  of  Chlorosis  and  of  Organic  Mitral 
disease. — The  differential  diagnosis  of  a  primary  cardiac  lesion  and 
of  the  chlorotic  heart  is  not  always  easy.  In  the  earlier  stages  of 
chlorosis  in  which  a  pulmonary  systolic  murmur  is  alone  present, 
there  is  usually  no  difficulty.  It  is  in  the  advanced  stages  when 
the  heart  cavities  become  dilated,  when  murmurs  are  developed  at 
the  mitral  and  tricuspid  orifices  that  the  chief  difficulty  of  diagnosis 
occurs.  In  cases  of  this  kind,  the  patient  suffers  from  palpitation 
and  shortness  of  breath,  and  oedema  of  the  feet  may  be  present. 
The  condition  may  consequently  be  easily  mistaken  by  an  inexperi- 
enced observer  for  a  case  of  primary  heart  disease.  But  the  pro- 
found anaemia  and  the  condition  of  the  blood  (the  marked  deficiency 
of  haemoglobin)  at  once  suggest  the  true  nature  of  the  case.  It  is 
only  in  those  cases  in  which  there  is  a  history  of  previous  rheu- 
matism, or  where  there  is  reason  to  suppose  that  the  heart  was 
affected  before  the  bloodless  condition  developed,  that  the  diagnosis 
presents  any  real  difficulty. 

In  doubtful  cases,  the  effects  of  treatment  are  most  important  in 
deciding  the  true  nature  of  the  condition.  Chlorosis  is,  as  I  have 
already  stated,  easily  cured  by  appropriate  treatment,  and  with  the 
disappearance  of  the  anaemia,  the  heart  symptoms  and  physical 
signs  subside  and  gradually  disappear.  With  the  supply  of  iron  to 
the  blood,  the  nutritive  alterations  and  fatty  changes  in  the  heart 
muscle  disappear,  the  dilatation  subsides  and  the  heart  becomes 
normal.  It  must  be  remembered  that  while  in  some  cases  fatty 
degeneration  of  the  heart  muscle  is  a  very  grave  disease,  in  others, 
as  in  aggravated  and  long-continued  cases  of  chlorosis,  it  is  emi- 
nently curable.  It  cannot  be  too  forcibly  insisted  on  that  the  prog- 
nosis in  cases  of  fatty  heart  depends  entirely  upon  the  cause 
of  the  condition — whether  that  cause  is  removable  by  treatment 
or  not. 

The  Differential  Diagnosis  of  Chlorosis  and  Ulcerative  En- 
docarditis.— This  rarely  presents  any  difficulty,  although  the  two 
conditions  are,  as  regards  some  of  their  symptoms,  very  similar.  In 
both  diseases,  a  profound  condition  of  anaemia,  a  greenish-yellow 
or  lemon-yellow  tint  of  the  skin,  cardiac  murmurs,  a  dilated  and 
unduly  irritable  condition  of  the  heart,  with  arterial  murmurs,  a 
jerking  visible  condition  of  the  pulse  and  a  distended  and  pulsating 


46  DISEASES   OF   THE   BLOOD. 

condition  of  the  veins  in  the  neck  may  be  present.  In  ulcerative 
endocarditis  there  is  usually  more  or  less  fever,  and  some  cases  of 
chlorosis  are,  as  I  have  already  stated,  attended  with  slight  and 
temporary  pyrexia. 

The  chief  points  of  distinction  are  : — The  age  and  sex  of  the 
patient ;  the  condition  of  the  blood  ;  the  exact  condition  of  the 
heart ;  the  character  of  the  febrile  disturbance  ;  the  condition  of  the 
spleen  ;  and  the  presence  or  absence  of  symptoms  indicative  of 
embolic  infarction. 

Chlorosis  is,  as  we  have  seen,  essentially  a.  disease  of  young 
women.  Ulcerative  endocarditis  may,  of  course,  occur  at  the  same 
age,  but  it  is  comparatively  speaking  uncommon  in  young  women. 
The  sex  of  the  patient  and  the  age  of  the  patient  are  consequently 
of  some  importance. 

In  chlorosis,  the  anaemia,  and  especially  a  deficiency  of  haemo- 
globin, are  the  fundamental  features  of  the  case,  while  the  altered 
condition  of  the  heart  is  secondary.  But  in  ulcerative  endocarditis, 
the  anaemia  is  secondary  to  and  the  result  of  the  cardiac  lesion. 
The  history  of  the  case  and  the  way  in  which  the  anaemia  has  de- 
veloped are  consequently  of  importance  for  the  purposes  of  diagnosis. 
Further  in  some  cases  of  ulcerative  endocarditis,  staphylococci  or 
other  micro-organisms  can  be  detected  in  the  blood  by  staining  or 
cultivation. 

In  most  cases  of  ulcerative  endocarditis  the  cardiac  lesion  and 
the  cardiac  symptoms  are  far  greater  than  can  reasonably  be 
accounted  for  by  the  degree  of  anaemia  which  is  present  ;  whereas 
in  chlorosis  the  reverse  is  the  case — the  cardiac  symptoms  and  the 
degree  of  cardiac  dilatation  are  more  or  less  proportionate  to  the 
degree  of  the  anaemia  and  the  length  of  time  it  has  existed. 

In  chlorosis,  fever  is  rare  except  as  the  result  of  some  well- 
marked  complication  such  as  thrombosis  of  the  veins  of  the  leg  ; 
while,  in  ulcerative  endocarditis,  fever  is  almost  always  present  and 
is  usually  a  striking  feature  of  the  case. 

In  ulcerative  endocarditis,  the  spleen  is  usually  enlarged  and 
symptoms  indicative  of  embolic  infarctions  and  of  peripheral  in- 
flammations, the  result  of  minute  emboli,  are  often  developed. 
These  conditions  are  absent  in  chlorosis,  though  venous  thromboses, 
especially  in  the  calf,  sometimes  occur. 

Further,  in  cases  of  ulcerative  endocarditis,  it  is  obvious  that  the 
patient  is  seriously  ill  ;  the  general  condition  is  suggestive  and  in- 
dicative of  gravity  and  danger.  This  is  rarely  the  case  in  chlorosis, 
although  in  any  profound  condition  of  anaemia,  the  patient  may  look 
extremely  ill  and  manifest  great  exhaustion  after  effort.     I  recently 


CHLOROSIS.  47 

had  in  hospital  a  case  in  point — a  profound  case  of  chlorosis — in 
which  the  patient  walked  some  distance  to  the  hospital.  On 
admission,  she  looked  extremely  ill  and  her  condition  was  sug- 
gestive of  great  danger,  but  a  few  days'  rest  in  bed  and  appropriate 
treatment  were  immediately  followed  by  marked  improvement  and 
a  striking  change  in  the  appearance  of  the  case. 

Lastly,  and  this  is  a  most  important  point,  the  effects  of  treat- 
ment are  of  the  greatest  diagnostic  value. 

The  Differential  Diagnosis  of  Chlorosis  and  Pernicious 
Anaemia. — When  the  observer  has  satisfied  himself  that  the  anaemia 
is  primary,  that  there  is  no  obvious  disease  in  any  of  the  organs  to 
account  for  it,  and  that  the  bloodlessness  is  the  chief  clinical 
characteristic  of  the  case,  the  question  arises  whether  the  case  is 
one  of  chlorosis  or  of  pernicious  anaemia.  In  the  great  majority 
of  cases  there  is  no  difficulty  in  deciding  this  point. 

The  chief  points  to  which  attention  should  be  directed  in  order 
to  decide  the  question  are  : — (i.)  The  age  and  sex  of  the  patient. — 
Pernicious  anaemia  rarely  occurs  in  young  women,  while  chlorosis 
is  almost  exclusively  a  disease  of  young  women.  In  my  314  cases 
of  typical  chlorosis,  no  case  occurred  after  the  age  of  33  (though  I 
have  seen  three  or  four  cases,  apparently  of  primary  anaemia  of 
the  chlorotic  type,  in  middle-aged  or  old  women),  and  only  1 1 
cases  after  the  age  of  28  ;  while  in  my  series  of  45  cases  of 
pernicious  anaemia  only  3  cases  occurred  below  the  age  of  28. 

(2.)  The  condition  of  the  blood. —  In  pernicious  anaemia,  the  red 
blood  corpuscles  are  enormously  reduced  in  number  ;  though  the 
total  amount  of  haemoglobin  is  often  markedly  diminished,  the 
richness  in  haemoglobin  of  the  individual  red  blood  corpuscles  is 
usually  equal  to  or  above,  the  normal ;  the  red  blood  corpuscles  do 
not  form  rouleaux,  and  they  present  marked  variations  in  size  and 
shape.  Whereas,  in  chlorosis  the  red  blood  corpuscles  may  be 
almost  up  to  the  normal  average  number,  or  in  the  more  severe 
cases  only  moderately  decreased  in  number  ;  though  in  exceptional 
cases  they  are  greatly  reduced,  the  lowest  figure  I  have  met  with 
being  1,425,000  per  cubic  millimetre  (average  in  my  cases,  3,437,300 
per  cubic  millimetre).  The  total  haemoglobin  is  not  only  decreased 
but  the  richness  in  haemoglobin  of  the  individual  red  blood 
corpuscles  is  markedly  below  the  normal — average  49.4  per  cent, 
in  my  own  cases.  Apart  from  the  pallor  of  the  red  blood  corpuscles 
and  the  fact  that  many  of  the  red  corpuscles  are  somewhat  smaller 
than  normal,  the  microscopical  characters  of  the  blood  do  not  as  a 
rule  present  any  marked  or  characteristic  alterations,  though  a 
moderate  degree  of  poikilocytosis  is  common.     The  extreme  varia- 


48  DISEASES   OF   THE   BLOOD. 

tions  in  size  and  shape  which  are  so  characteristic  of  pernicious 
anaemia  are  comparatively  rarely  present  in  chlorosis. 

The  concentration  of  the  haemoglobin  in  localised  parts  of  the 
red  corpuscles  (apparent  nucleation)  which  is  such  a  constant 
feature  in  pernicious  anaemia  is  rarely  seen,  at  all  events  in  a  marked 
degree,  in  chlorosis. 

Nucleated  red  corpuscles  which  frequently  occur  in  pernicious 
anaemia,  though  they  may  only  be  present  in  small  number,  are 
very  rarely  met  with  in  chlorosis  (only  in  very  severe  cases  of  long 
duration). 

In  pernicious  anaemia  the  blood  coagulates  less  rapidly  than  in 
health,  the  blood-plates  are  usually  diminished  in  number,  some- 
times markedly  so,  and  the  fibrin  network  is  deficient ;  whereas  in 
chlorosis  the  blood-plates  and  Max  Schultze's  granular  masses  are 
usually  more  numerous  than  in  health,  and  the  fibrin  network  is 
usually  abundant. 

(3.)  The  therapeutic  effect  of  iron. — In  pernicious  anaemia,  iron 
usually  produces  no  improvement,  in  fact  in  many  cases  it  seems 
to  do  harm  rather  than  good  ;  while  in  the  vast  majority  of  cases 
of  chlorosis  the  patients  rapidly  improve  under  the  administration 
of  iron  (together  with  rest  in  bed,  etc.),  provided  always  that  the 
iron  is  given  in  sufficiently  large  doses  and  that  the  gastro-intestinal 
tract  is  in  a  healthy  condition. 

(4.)  The  presence  of  pyrexia.  —  In  chlorosis,  fever  is  rarely 
developed  except  as  the  result  of  some  intercurrent  complication 
such  as  thrombosis  of  the  veins  of  the  leg ;  whereas  in  pernicious 
anaemia  intercurrent  and  apparently  causeless  attacks  of  pyrexia 
(true  anaemic  fever)  are  of  frequent  occurrence  and  of  considerable 
diagnostic  value. 

(5.)  The  condition  of  the  urine. — This,  though  an  uncertain 
guide,  is,  in  some  cases,  of  considerable  diagnostic  importance. 
In  chlorosis,  the  urine  is  usually  normal  in  colour  or  paler  than 
normal.  In  pernicious  anaemia,  the  urine  may  be  of  normal  colour 
or  pale,  but  is  apt  from  time  to  time  (during  the  temporary  exacer- 
bations) to  be  darker  than  normal. 

Prognosis. 

In  cases  of  chlorosis  the  prognosis  is  eminently  favourable, 
unless  the  disease  should  happen  to  be  attended  with  some  grave 
complication,  such  as  ulceration  of  the  stomach,  thrombosis  of  the 
cerebral  sinuses,  etc.  There  are  few  diseases  which  are  more 
amenable  to  treatment  than    chlorosis.     Nevertheless,    a    marked 


CHLOROSIS.  49 

degree  of  chlorosis  should  never  be  made  light  of;  for  so  long  as 
the  profound  anaemia  continues,  complications  of  a  serious  kind  are 
apt  to  be  developed.  I  have  already  referred  to  the  frequency  with 
which  ulceration  of  the  stomach  is  developed  in  cases  of  chlorosis  ; 
consequently  the  possibility  of  the  occurrence  of  this  serious  com- 
plication should  always  be  kept  in  view.  Further,  in  a  certain 
proportion  of  cases  of  chlorosis,  thrombosis  of  the  veins  is  developed. 
When  the  tibial  or  femoral  vein  is  affected,  the  condition  is  almost 
always  recovered  from  ;  but  in  rare  cases  the  cerebral  veins  may 
become  thrombosed,  or  a  portion  of  clot  from  the  thrombosed 
femoral  vein  may  be  detached  and  may  be  swept  through  the 
circulation  with  the  production  of  fatal  plugging  of  the  pulmonary 
artery.  Again,  the  development  of  an  acute  disease  in  the  course 
of  chlorosis,  such,  for  example,  as  endocarditis  or  acute  croupous 
pneumonia,  is  always  a  serious  matter.  An  example  in  point 
occurred  a  few  years  ago  in  my  hospital  practice.  A  young  woman 
who,  for  several  months,  had  suffered  from  profound  chlorosis,  was 
admitted  suffering  from  an  attack  of  acute  croupous  pneumonia. 
Although  the  lung  lesion  was  only  moderate  in  extent,  the  patient 
died  notwithstanding  the  most  careful  treatment.  The  fatal  issue 
was,  I  believe,  mainly  due  to  the  anaemic  condition  of  the  blood 
and  the  chlorotic  condition  of  the  heart.  In  acute  croupous 
pneumonia,  the  prognosis,  as  every  one  knows,  largely  turns  upon 
the  condition  of  the  heart.  The  enfeebled  and  dilated  (and  in 
some  cases  fatty)  heart  of  chlorosis  is  unable  to  bear  the  strain  of 
a  severe  attack  of  continued  fever  or  of  a  severe  attack  of  acute 
croupous  pneumonia. 

Further,  it  would  appear  that  chlorosis  predisposes  to  the 
occurrence  of  endocarditis.  Acute  nephritis  and  pernicious  anaemia 
are  also,  it  is  said,  occasionally  developed  in  the  course  of  the 
disease. 

For  the  reasons  just  stated,  it  will  be  apparent  that  it  is  emi- 
nently advisable  to  cure  cases  of  chlorosis  as  speedily  as  possible, 
and,  so  long  as  the  chlorotic  condition  continues,  to  guard  the 
patient  as  carefully  as  possible  from  exposure  to  the  causes  of 
acute  febrile  disease  and  from  conditions  likely  to  produce  inter- 
current complications. 

But  although  in  the  great  majority  of  cases  the  prognosis  is 
eminently  favourable  and  the  disease  rapidly  cured  by  appropriate 
treatment,  this,  it  must  be  remembered,  is  not  invariably  the  case. 
In  a  small  proportion  of  uncomplicated  cases  the  disease  is  most 
obstinate. 

Further,  it  must  be  remembered  that  in  most  cases  of  chlorosis 

D 


50  DISEASES   OF   THE    BLOOD. 

there  is  a  strong  tendency  to  relapse  and  recurrence.  Hence  the 
importance,  after  the  disease  has  been  temporarily  cured,  of  per- 
sistent care  and  watchfulness  and  of  continued  treatment — the 
continued  administration  of  iron  in  small  doses.  After  the  age  of 
25,  provided  that  no  complications  are  present,  the  disease  usually 
cures  itself. 

Treatment. 

In  the  treatment  of  chlorosis,  the  essential  point  is  to  supply 
iron  to  the  blood.  I  will  presently  refer  to  the  method  which  in 
my  experience  is  most  effectual  for  this  purpose.  But  before  doing 
so,  let  me  say  a  word  or  two  with  regard  to  the  general  manage- 
ment and  hygienic  treatment. 

In  all  cases  in  which  the  bloodlessness  is  marked,  I  attach  the 
greatest  importance  to  keeping  the  patient  persistently  at  rest  in 
bed.  One  reason  why  the  disease  is  so  much  more  easily  cured  in 
hospital  than  in  private  practice  is,  I  think,  because  the  hospital 
patients  are  kept  in  bed.  The  absolute  rest  in  the  recumbent  posi- 
tion removes  all  strain  from  the  heart  (a  most  important  point)  and 
aids  the  recuperative  powers.  In  chlorosis,  anything  which  excites 
the  body  or  mind  and  which  is  apt  to  suddenly  accelerate  the  heart's 
action  should  be  avoided. 

While  the  patient  is  lying  in  bed,  her  surroundings  should  be 
as  bright  and  pleasant  as  possible.  It  is  very  desirable  that  she 
should  have  plenty  of  fresh  air  and  an  abundance  of  sunlight  when 
it  can  be  obtained.  There  can,  I  think,  be  no  question  that  sun- 
light hastens  the  cure. 

The  temperature  of  the  bedroom  should  be  kept  about  55, 
rather  on  the  cool  than  on  the  hot  side. 

The  food  should  be  nutritious  and  easily  digestible.  When 
there  are  no  dyspeptic  symptoms,  an  ordinary  mixed  diet,  consist- 
ing of  milk,  milk  foods,  fish,  white  meat,  butcher  meat,  a  moderate 
amount  of  vegetables,  and  fruit,  may  be  allowed.  Some  chlorotic 
patients  seem  to  have  a  special  liking  for  oranges  and  lemons  ; 
they  sometimes  have  a  craving  for  acids.  As  I  have  already 
pointed  out,  it  has  been  suggested  that  the  disease  is  the  result 
of  a  deficiency  of  hydrochloric  acid  in  the  gastric  juice.  While 
I  see  no  reason  to  accept  this  view  (or  indeed  to  believe  that  in 
most  cases  of  chlorosis  there  is  any  deficiency  of  hydrochloric 
acid;,  I  nevertheless  think  it  advisable  to  allow  the  patient  to  satisfy 
this  natural  craving  when  it  is  present. 

The  function  of  the  bowels  should  be  carefully  regulated.  This 
is  a  most  important  point,  for  although  I  do  not  agree  with  the 


CHLOROSIS.  51 

late  Sir  Andrew  Clark  in  thinking  that  the  chlorotic  condition  is 
the  direct  result  of  the  constipation  with  which  it  is  so  often 
associated,  careful  regulation  of  the  bowels  seems  to  aid  recovery. 
The  object  of  the  physician  should  be  to  see  that  the  bowels  are 
not  only  evacuated  daily,  but  that  the  evacuation  is  sufficiently 
copious.  Cascara,  or  aloin  with  nux  vomica,  ipecacuanha  and 
belladonna  may  be  given  each  night,  or  some  purgative  mineral 
water  first  thing  in  the  morning  in  sufficient  quantity  to  produce  a 
copious  and  soft  but  not  liquid  motion.  The  tendency  which  iron 
has  to  produce  constipation  should  be  remembered  ;  and  in  pre- 
scribing a  laxative  it  is  well  to  remember  that  the  constipation  in 
chlorosis  probably  depends,  in  part  at  least,  upon  loss  of  muscular 
tone,  and  to  select  a  drug  which  stimulates  the  muscular  coat  of 
the  intestine. 

When  dyspeptic  symptoms  are  prominent,  it  is  of  great  im- 
portance to  restore  the  stomach  and  gastro-intestinal  tract  to  a 
normal  healthy  condition.  This  is  an  important  point  in  the  treat- 
ment. In  some  of  the  dyspeptic  cases,  iron  is  badly  borne,  or 
at  all  events  it  cannot  be  given  as  freely  as  in  other  cases  of 
chlorosis  in  which  there  is  no  dyspepsia.  It  must,  however,  be 
remembered  that  the  dyspepsia  which  is  so  frequently  associated 
with  chlorosis  may  be  due  to  different  causes.  In  most  cases  the 
anaemia  is  the  cause  of  the  stomach  disorder.  In  such  cases,  the 
dyspeptic  symptoms  disappear  with  the  removal  of  the  chlorosis. 
As  a  matter  of  experience,  I  find  that  in  those  cases  of  chlorosis  in 
which  the  tongue  is  flabby,  furred  and  indented  by  the  teeth,  in 
which  the  breath  is  foul  and  the  patient  troubled  with  flatulence,  a 
preliminary  course  of  alkalies  is  often  most  helpful.  In  my  experi- 
ence, there  is  nothing  more  efficacious  than  a  combination  of 
bicarbonate  of  potash,  bicarbonate  of  soda,  aromatic  spirits  of 
ammonia,  tincture  of  rhubarb  and  infusion  of  calumba.*  With 
this  alkaline  mixture  given  before  meals,  a  tonic  containing  hydro- 
chloric acid,  nux  vomica  and  gentian  may  be  given  after  meals. 

As  soon  as  the  tongue  begins  to  clean,  iron  should  be  freely 
given  ;  but  in  most  cases  I  find  that  the  iron  may  be  given  from 

*  This  alkaline  mixture  which  I  give  largely  and  with  great  advantage  in 
cases  of  chronic  gastritis  and  flatulent  dyspepsia  is  as  follows  : — 
Re         Potassi  Bicarb., 
Sodii  Bicarb., 
Sp.  Amm.  Arom.  aa  3iii. 
Tr.  Rhtei  3iss. 
Inf.  Calumba;  ad  svi. 

Sig. — A  tablespoonful  in  water  three  times  daily  twenty  minutes  before  meals. 


52  DISEASES   OF   THE    BLOOD. 

the  first  together  with  these  other  remedies.  In  some  cases  I  give 
a  bitter  tonic  before  meals  and  the  iron  after  meals.  This  is,  I 
think,  the  most  effective  plan  of  treatment  in  those  cases  in  which 
the  dyspeptic  symptoms  seem  to  be  entirely  the  result  of  the 
chlorotic  condition.  Dr  Lauder  Brunton  has  pointed  out  that  in 
cases  of  dyspeptic  chlorosis  the  astringent  preparations  of  iron 
are  often  better  borne  than  the  ordinary  forms  ;  but,  speaking  for 
myself,  I  find  that  Robertson's  Blaud's  pill  capsules  are  usually 
well  borne  even  in  the  dyspeptic  cases.  I  have  found  this  pre- 
paration of  iron  far  more  efficacious  than  any  other  which  I  have 
hitherto  employed. 

In  those  cases  in  which  the  stomach  is  ulcerated,  the  diet  must 
of  course  be  carefully  regulated.  It  should  consist  of  milk,  beef 
extracts,  milk  foods  and,  when  the  symptoms  are  severe,  peptonised 
milk  alone.  Raw  beef  juice  or  finely  pounded  raw  meat  is,  in  some 
of  these  cases,  well  borne.  In  those  cases  in  which  the  stomach  is 
very  irritable,  I  have  found  the  greatest  advantage  from  rectal 
feeding.  In  many  cases  a  blister  applied  over  the  region  of  the 
stomach  is  beneficial.  The  bowels  should,  of  course,  be  carefully 
regulated  in  the  manner  that  I  have  already  described,  and  iron  and 
arsenic  should  be  given  internally. 

In  cases  of  chlorosis,  the  essential  part  of  the  treatment  is,  as  I 
have  already  mentioned,  the  administration  of  iron  ;  and  one  great 
secret  of  success  is  to  give  a  sufficient  quantity  of  iron.  It  matters 
perhaps  comparatively  little  what  the  particular  preparation  is,  pro- 
vided only  that  enough  of  it  is  given,  but  some  preparations  are 
better  borne  and  are  more  effective  than  others.  Personally,  I  have 
been  most  successful  with  Robertson's  Blaud's  pill  capsules.* 
Robertson's  capsules  are  made  of  different  strengths,  corresponding 
to  one,  two  and  three  Blaud's  pills.  Unless  there  is  any  reason  to 
the  contrary,  I  begin  with  the  No.  3  capsule,  which  contains  the 
same  amount  of  carbonate  of  iron  as  three  Blaud's  pills,  and  give 
one  capsule  three  times  daily,  after  meals  ;  but  I  do  not  stop  there  ; 
I  gradually  increase  the  dose.     During  the  first  week  I  give  one 


*  .Messrs  Robertson  inform  me  that  they  attribute  the  medicinal  value  of  the 
preparation  to  the  use  of  the  dried  salts  and  the  medium  used  for  forming  the 
mass.  The  disintegration  being  gradual,  the  nascent  ferrous  carbonate  is  slowly 
formed  in  the  stomach  and  is  as  quickly  absorbed  by  the  system,  and  hence  the 
good  results.  That  the  ferrous  carbonate  is  formed  after  the  administration  is, 
they  say,  also  proved  by  the  slight  aperient  effect  which  the  capsules  have, 
owing  to  the  formation  of  an  alkaline  sulphate.  They  claim  that  this  aperient 
action  does  away  with  the  necessity  of  patients  having  to  take  an  aperient ;  but 
with  this  opinion  my  experience  does  not  altogether  agree. 


CHLOROSIS.  53 

(No.  3)  capsule,  three  times  daily ;  during  the  second  week,  two 
(No.  3)  capsules  ;  during  the  third  week,  three  (No.  3)  capsules  ; 
and  during  the  fourth  and  succeeding  weeks,  four  (No.  3)  capsules 
three  times  daily — equivalent  to  thirty-six  Blaud's  pills  per  diem.  In 
some  cases  I  have  given  much  larger  doses  even  than  this.  In  one 
case  which  was  recently  under  treatment  in  hospital,  I  gave,  as  an  ex- 
periment, ten  No.  3  capsules  three  times  daily — equivalent  to  ninety 
Blaud's  pills  per  diem.  Such  enormous  doses  are  in  the  great 
majority  of  cases  altogether  unnecessary  ;  four  (No.  3)  capsules, 
three  times  daily  (corresponding  to  twelve  ordinary  Blaud's  pills, 
three  times  daily),  are  abundantly  sufficient. 

In  addition  to  the  iron,  I  often  prescribe  arsenic  ;  but  I  do  not 
attach  any  great  importance  to  the  influence  of  the  arsenic  in 
chlorosis,  except  in  the  rare  cases  in  which  the  red  blood  corpuscles 
are  markedly  reduced  in  number  ;  in  such  cases  arsenic  is,  I  think, 
of  great  value  In  the  great  majority  of  cases  of  chlorosis,  iron  is  a 
far  more  efficacious  remedy  than  arsenic.  In  those  cases  in  which 
I  think  it  advisable  to  prescribe  arsenic,  I  usually  give  two  minims 
of  Fowler's  solution  three  times  a  day  for  the  first  week  ;  three 
minims  the  second  ;  four  minims  the  third  ;  and  five  minims  three 
times  daily  during  the  fourth  and  succeeding  weeks. 

If  the  plan  of  treatment  which  I  have  now  described  is  faith- 
fully and  diligently  carried  out,  there  is  in  my  experience  very  rarely 
any  difficulty  in  speedily  curing  even  the  most  severe  and  obstinate 
cases  of  chlorosis,  provided  of  course  that  no  grave  or  serious  com- 
plications are  present.  I  have,  I  think,  obtained  greater  credit  and 
reputation  from  the  treatment  of  severe  and  obstinate  cases  of 
chlorosis,  both  in  private  and  hospital  practice,  than  from  the  treat- 
ment of  any  other  disease.  I  rarely  fail  to  cure  even  the  most 
severe  cases  in  the  course  of  from  four  to  six  weeks'  time.  The 
points  on  which  I  lay  most  stress  are  : — (1)  rest  in  bed  ;  (2)  careful 
regulation  of  the  diet  and  bowels  ;  and  (3)  the  administration  of 
large  doses  of  iron. 

Speaking  theoretically,  the  iron  should  be  continued  in  full 
doses  until  the  haemoglobin,  as  estimated  by  the  hsemoglobinometer, 
reaches  the  normal  amount  (85  to  90  per  cent,  as  estimated  by 
Gowers'  instrument).  This  I  consider  a  most  important  point.  It 
should  always  be  aimed  at ;  for  no  case  of  chlorosis  is  really  cured 
until  the  haemoglobin  has  reached  the  normal  amount,  but  it  is  often 
difficult  to  attain  to  in  actual  practice.  One  has  often  to  be  content 
with  a  percentage  of  from  65  to  75  per  cent,  (as  estimated  by 
Gowers'  instrument)  After  the  case  is  cured  (or  apparently  cured) 
the  iron  should  still  be  persistently  administered  for  several  months 


54  DISEASES   OF   THE    BLOOD. 

in  smaller  doses — one  No.  ,3  capsule,  equal  to  three  Blaud's  pills, 
three  times  a  day. 

There  are,  of  course,  many  other  preparations  of  iron  which 
are  very  effective.  Griffith's  mixture,  the  saccharine  carbonate, 
the  sulphate,  the  bi-palatinoids  of  Oppenheimer,  the  oxalate,  the 
lactate,  are  all  admirable  preparations  ;  but  with  none  of  them  have 
I  obtained  such  satisfactory  results  as  with  Robertson's  Blaud's  pill 
capsules. 

In  children,  in  whom  a  profound  anaemia  exactly  corresponding 
to  the  chlorosis  of  young  women  is  occasionally  met  with,  the 
saccharine  carbonate  is  perhaps  the  most  effective  remedy  ;  it  is 
easily  taken  and  should  be  freely  given.  A  very  convenient  way  is 
to  give  it  mixed  with  brown  Demerara  sugar. 

In  some  of  the  dyspeptic  cases,  I  have  found  a  combination  of 
the  tincture  of  the  perchloride  of  iron  with  sulphate  of  magnesia  a 
very  efficacious  form. 

In  the  anaemia  of  young  males,  which  in  my  experience  is  often 
attended  with  emaciation  and  dyspeptic  symptoms,  and  which 
appears,  in  some  cases  at  all  events,  to  be  of  the  chlorotic  type, 
this  combination  of  perchloride  of  iron  and  sulphate  of  magnesia  is, 
I  think,  particularly  efficacious.  In  passing,  I  may  also  say  that 
this  is  a  most  useful  remedy  in  cases  in  which  sores  which  are 
difficult  to  heal  break  out  about  the  nose,  and  in  cases  of  recurring 
boils.  In  some  of  these  conditions,  the  symptoms  are  perhaps  due 
to  absorption  into  the  blood  of  poisonous  products  developed  in  the 
intestine.  In  cases  of  this  kind,  constipation  is  often  a  prominent 
symptom.  The  combination  of  perchloride  of  iron  and  sulphate  of 
magnesia  acts  both  as  a  laxative,  an  intestinal  disinfectant  and  as  a 
blood  tonic. 

In  the  treatment  of  chlorosis,  sulphur  is  also  a  useful  remedy; 
its  beneficial  effect  is  probably  due  to  its  action  as  a  laxative. 

Other  remedies  which  have  been  recommended  for  the  treat- 
ment of  chlorosis  are  oxygen  inhalations  and  the  administration  of 
bone-marrow.  I  have  no  personal  experience  to  offer  with  regard 
to  either  of  them.  I  am  so  successful  with  the  rest-iron  plan  of 
treatment,  which  I  have  described  above,  that  I  have  never 
found  it  necessary  to  give  any  other  plan  of  treatment  a  prolonged 
trial. 

In  the  course  of  three  or  four  weeks,  the  patient  may  be  allowed 
to  get  out  of  bed  and  to  pass  part  of  the  day  on  a  sofa  or  to  take 
carriage  exercise.  In  cases  of  chlorosis  walking  exercise  is,  I  think, 
better  avoided,  so  long,  at  all  events,  as  the  heart  symptoms — the 
shortness  of  breath   on    exertion,  the    palpitation,   etc. — continue. 


CHLOROSIS.  55 

As  the  colour  returns  and  the  haemoglobin  increases,  the  patient 
may  gradually  be  allowed  to  return  to  her  ordinary  mode  of  life. 

During  the  earlier  part  of  the  treatment  while  the  patient  is 
confined  to  bed,  massage  is  often  a  valuable  adjunct  to  the  treat- 
ment. It  promotes  the  muscular  nutrition  and  gives  the  patient,  as 
it  were,  a  sufficient  amount  of  exercise  without  throwing  any  undue 
strain  upon  the  heart. 

It  is  essential  to  remember  that  chlorosis  is  a  condition  which 
is  very  apt  to  relapse.  As  I  have  already  stated,  the  iron  should 
be  persistently  continued  for  some  time — several  months  at  least — 
after  the  case  is  apparently  cured  ;  and  after  all  treatment  has  been 
suspended,  the  patient  should  be  closely  watched  for  a  year  or  two 
at  least.  If  any  indications  of  a  relapse  (such  as  pallor,  breathless- 
ness,  palpitation,  etc.)  again  develop,  another  course  of  iron  should 
be  immediately  prescribed  ;  but,  provided  that  the  onset  of  the 
relapse  is  recognised  at  an  early  stage,  it  is  rarely  necessary  to  con- 
fine the  patient  to  bed.  Careful  regulation  of  the  bowels,  avoidance 
of  cardiac  strain  and  the  administration  of  iron  are,  in  such  circum- 
stances, usually  all  that  are  required  to  effect  a  cure. 

I  have  described  the  treatment  of  chlorosis  in  considerable 
detail  ;  it  is  an  important  subject,  for  the  disease  is  very  common 
and  it  is  a  most  satisfactory  disease  to  treat.  Niemeyer  used  to  say 
that  he  gained  great  credit  in  practice  by  the  successful  administra- 
tion of  Blaud's  pills  ;  and,  as  I  have  already  stated,  my  personal 
experience  is  identical  with  his  on  this  point. 

To  sum  up,  the  essential  points  in  the  treatment  of  chlorosis  are 
in  my  opinion  persistent  rest  in  bed  in  a  well-ventilated  and  sunny 
room,  careful  regulation  of  the  diet  and  bowels,  and  above  all  the 
administration  of  large  doses  of  iron,  Robertson's  Blaud's  pill 
capsules  being  in  my  experience  more  effective  than  any  other 
preparation. 


PERNICIOUS    ANEMIA. 

Definition  or  Short  Description.  —  This  very  interesting 
disease,  to  which  the  synonyms  Idiopathic  anaemia,  Essential 
anaemia,  Progressive  pernicious  anaemia,  etc.,  have  been  applied, 
is  characterised  by  profound  anaemia,  which  usually  develops 
insidiously  and  without  apparent  cause.  It  tends  to  pursue  a 
progressive  course  and  with  rare  exceptions  ultimately  terminates 
in  death. 

The  essential  feature  of  pernicious  anaemia  is  the  great  diminu- 
tion in  the  number  of  the  red  blood  corpuscles.  The  total  amount 
of  haemoglobin  in  the  blood  is  also  markedly  decreased,  but  the 
diminution  of  the  haemoglobin  is  usually  less  than  that  of  the 
corpuscles  ;  in  fact,  the  richness  of  the  individual  corpuscles  in 
haemoglobin  is  in  most  typical  cases  considerably  above  the  normal. 

The  essential  and  primary  lesion  in  pernicious  anaemia  seems  to 
be  a  destruction  of  the  red  blood  corpuscles.  Dr  William  Hunter, 
whose  observations  have  added  so  much  to  our  knowledge  of  the 
pathology  of  the  disease,  thinks  that  the  blood  destruction  is  due 
to  a  poison  absorbed  from  the  gastro-intestinal  tract ;  and  that  this 
poison  leads  to  the  rapid  destruction  of  the  red  blood  corpuscles 
in  the  portal  circulation  (more  especially  in  the  spleen  and  liver) 
and  at  the  same  time  exerts  a  disturbing  influence  upon  the  liver 
cells.  Some  years  ago,  I  ventured  to  suggest  to  Dr  Hunter  that,  if 
this  view  were  correct,  the  disease  might  be  appropriately  termed 
gastro-intestinal-hepatic  anaemia. 

Historical  Note. — The  celebrated  Dr  Addison  of  Guy's  Hos- 
pital, the  discoverer  of  Addison's  disease,  was  the  first  to  give  a 
complete  description  of  the  disease  ;  he  termed  it  idiopathic  ancemia. 
Addison's  description  was  published  in  the  year  1 85 5- 

Though  well  known  to  Dr  Wilks  and  the  physicians  of  Guy's 
Hospital,  it  was  for  a  time  lost  sight  of  until  it  was  redescribed  by 
Professor  Biermer  of  Zurich  in  the  year  1872.  In  1876  and  1877 
I  published  two  clinical  lectures  on  the  subject  in  the  Medical 
Times  and  Ga/x-tte,  and  a  series  of  cases  in  the  "  Edinburgh 
Medical  Journal";  in  the  latter  communication  I  figured  the  blood 


PERNICIOUS   ANAEMIA.  57 

changes  and  directed  attention  to  the  value  of  arsenic  in  the  treat- 
ment of  the  disease.  In  Vol.  xxvi.  Guy's  Hospital  Reports 
(1882),  Dr  Pye-Smith  published  an  important  contribution  to  the 
subject,  in  which  he  gives  a  very  complete  resume  of  the  literature 
of  the  disease  up  to  that  date  and  an  abstract  of  102  cases  collected 
from  various  sources.  Of  recent  years,  numerous  cases  have  been 
recorded  and  our  knowledge  of  the  nature  and  causation  of  the 
disease  has  been  very  materially  increased. 

Before  considering  the  pathology  of  pernicious  anaemia  in  detail, 
it  will  perhaps  be  advisable  to  describe  the  clinical  history  of  the 
disease  and  the  morbid  alterations  which  are  present  in  the  bodies 
of  patients  who  have  died  of  the  disease. 


Clinical  History. 

Addison's  description  of  Pernicious  Anaemia.  —  Addison's 
description  of  pernicious  anaemia,  or  idiopathic  anaemia  as  he 
termed  it,  was  as  follows  : — 

"  For  a  long  period  I  had  from  time  to  time  met  with  a  very 
remarkable  form  of  general  anaemia  occurring  without  any  discover- 
able cause  whatever,  cases  in  which  there  had  been  no  previous 
loss  of  blood,  no  exhausting  diarrhoea,  no  chlorosis,  no  purpura,  no 
renal,  splenic,  miasmatic,  glandular,  strumous,  or  malignant  disease. 

"  Accordingly,  in  speaking  of  this  form  in  clinical  lectures,  I, 
perhaps  with  little  propriety,  applied  to  it  the  term  '  idiopathic '  to 
distinguish  it  from  cases  in  which  there  existed  more  or  less 
evidence  of  some  of  the  usual  causes  or  concomitants  of  the 
anaemic  state. 

"  The  disease  presented  in  every  instance  the  same  general 
character,  pursued  a  similar  course  and,  with  scarcely  a  single 
exception,  was  followed  after  a  variable  period  by  the  same  result. 

"  It  occurs  in  both  sexes  ;  generally,  but  not  exclusively,  beyond 
the  middle  period  of  life  ;  and,  so  far  as  I  at  present  know,  chiefly 
in  persons  of  a  somewhat  large  and  bulky  frame,  and  with  a  strongly- 
marked  tendency  to  the  formation  of  fat. 

"  It  makes  its  approach  in  so  slow  and  insidious  a  manner  that 
the  patient  can  hardly  fix  a  date  to  his  earliest  feeling  of  that 
languor  which  is  shortly  to  become  so  extreme.  The  countenance 
gets  pale,  the  whites  of  the  eyes  become  pearly,  the  general  frame 
flabby  rather  than  wasted  ;  the  pulse  perhaps  large,  but  remarkably 
soft  and  compressible,  and  occasionally  with  a  slight  jerk,  especially 
under  the  slightest  excitement.  There  is  an  increasing  indisposition 
to  exertion,  with  an  uncomfortable  feeling  of  faintness  or  breathless- 
ness  on  attempting  it ;  the  heart  is  readily  made  to  palpitate ;  the 
whole  surface  of  the  body  presents  a  blanched,  smooth,  and  waxy 


58  DISEASES   OF   THE    BLOOD. 

appearance ;  the  lips,  gums,  and  tongue  seem  bloodless  ;  the 
flabbiness  of  the  solids  increases  ;  the  appetite  fails  ;  extreme 
languor  and  faintness  supervene,  breathlessness  and  palpitations 
being  produced  by  the  most  trifling  exertion  or  emotion  ;  some 
slight  cedema  is  probably  perceived  about  the  ankles.  The  debility 
becomes  extreme  ;  the  patient  can  no  longer  rise  from  his  bed  ;  the 
mind  occasionally  wanders  ;  he  falls  into  a  prostrate  and  half-torpid 
state,  and  at  length  expires.  Nevertheless,  to  the  very  last,  and 
after  a  sickness  of  perhaps  several  months'  duration,  the  bulkiness 
of  the  general  frame  and  the  obesity  often  present  a  most  striking 
contrast  to  the  failure  and  exhaustion  observable  in  every  other 
respect. 

"With  perhaps  a  single  exception,  the  disease,  in  my  own 
experience,  resisted  all  remedial  efforts,  and  sooner  or  later 
terminated  fatally. 

"  On  examining  the  bodies  of  such  patients  after  death  I  have 
failed  to  discover  any  organic  lesion  that  could  properly  or  reason- 
ably be  assigned  as  an  adequate  cause  of  such  serious  consequences; 
nevertheless,  from  the  disease  having  uniformly  occurred  in  fat 
people,  I  was  naturally  led  to  entertain  a  suspicion  that  some  form 
of  fatty  degeneration  might  have  a  share  at  least  in  its  production  ; 
and  I  may  observe  that,  in  the  case  last  examined,  the  heart  had 
undergone  such  a  change,  and  that  a  portion  of  the  semilunar 
ganglion  and  solar  plexus,  on  being  subjected  to  microscopic 
examination,  was  pronounced  by  Mr  Quekett  to  have  passed  into 
a  corresponding  condition. 

"  Whether  any  or  all  of  these  morbid  changes  are  essentially 
concerned — as  I  believe  they  are — in  giving  rise  to  this  very 
remarkable  disease,  future  observation  will  probably  decide. 

"  The  cases  having  occurred  prior  to  the  publication  of  Dr 
Bennett's  interesting  essay  on  '  Leucocythaemia,'  it  was  not  deter- 
mined by  microscopic  examination  whether  there  did  or  did  not 
exist  an  excess  of  white  corpuscles  in  the  blood  of  such  patients." 

The  passage  is  taken  from  Addison's  classical  treatise  "  On  the 
Constitutional  and  Local  Effects  of  Disease  of  the  Suprarenal 
Capsules."  It  was  while  investigating  and  trying  to  detect  the 
cause  of  idiopathic  anaemia,  that  he  came  to  discover  the  disease 
of  the  suprarenal  capsules  which  bears  his  name. 

From  this  account,  it  will  be  seen  that  the  onset  of  pernicious 
anaemia,  or  idiopathic  anaemia  as  Addison  termed  it,  is,  as  a  rule, 
gradual  and  the  course  progressive,  though  cases  are  occasionally 
observed  in  which  the  onset  is  more  or  less  rapid  (in  one  of  my 
most  marked  cases  the  condition  had  developed  certainly  in  three 
and  probably  in  less  than  two  months'  time)  ;  that  in  most  cases 
the  condition  arises  without  any  apparent  cause  ;  that  it  is  chiefly 
characterised  by  debility  and  prostration,  increasing  pallor,  a  pro- 
foundly bloodless  condition  of  the  mucous  membranes  and  other 


PERNICIOUS   ANyEMIA.  59 

tissues  and  organs,  shortness  of  breath  and  palpitation,  and,  I  may 
add,  in  many  cases  by  slight  cedema  of  the  feet  and  eyelids,  retinal 
haemorrhages,  recurring  attacks  of  fever,  temporary  darkening  of 
the  urine,  and  it  may  be  of  jaundice,  etc.  Though,  in  the  advanced 
stages  of  the  disease,  some  swelling  of  the  feet  and  eyelids  is  of 
common  occurrence,  a  marked  degree  of  general  dropsy  and 
effusion  into  the  internal  cavities  are  rare. 

Let  us  take  a  typical  case  in  a  fully  developed  stage  and  con- 
sider some  of  the  symptoms  in  more  detail. 

Colour  of  the  skin  and  mucous  membranes.  —  In  well- 
marked  cases  of  pernicious  anaemia,  the  observer  is  at  once  struck 
by  the  remarkable  pallor  of  the  mucous  membranes  and  of  the 
skin.  The  skin  rarely  presents  the  white  pallor  which  is  seen  after 
haemorrhage  or  in  cases  of  Bright's  disease;  it  usually  has  a  lemon- 
yellow  or  canary-yellow  tint.  In  some  cases,  this  yellow  tint  is  so 
marked  that  the  patient  looks  as  if  he  were  jaundiced.  As  a 
matter  of  fact,  jaundice  is  in  many  cases  present ;  it  is  usually 
slight  in  degree,  though  in  rare  instances,  as  in   a  case  which   I 

00*0  ' 

recently  reported,*  the  jaundice  is  very  marked.  In  many  cases, 
the  yellow  tint  of  the  skin  is  not  due  to  jaundice.  In  some  cases 
it  is  probably  due  to  the  presence  of  a  pigment  derived  from  the 
destruction  of  red  blood  corpuscles.  This,  as  we  shall  presently  see, 
is  a  point  of  some  importance  from  an  etiological  point  of  view. 
In  some  cases  the  yellowness  of  the  conjunctiva  is  due,  as  I 
pointed  out  several  years  ago,  to  the  presence  of  little  deposits  of 
fat  beneath  the  conjunctiva.  In  those  cases  in  which  true  jaundice 
occurs,  the  whole  of  the  conjunctiva,  as  well  as  the  skin,  is  of  course 
stained  yellow. 

In  some  cases,  pigmented  patches  are  present  in  the  skin  ;  and, 
in  rare  cases,  this  pigmentation  is  so  marked  or  so  diffused  as  to 
suggest  the  presence  of  Addison's  disease.  I  have  met  with  five 
cases  in  which  the  skin  was  so  deeply  pigmented  as  to  give  rise  to 
the  suspicion  that  Addison's  disease  and  pernicious  anaemia  were 
combined.  In  two  of  these  cases  there  was  an  autopsy  and  in  both 
cases  the  suprarenal  capsules  were  normal.  In  two  cases  in  which 
there  was  no  post  mortem  the  pigmentation  of  the  skin  was,  I  think, 
due  to  the  arsenic  which  the  patient  had  been  taking  in  large  doses 
for  some  time  before  death. 

In  one  case  which  came  under  my  notice  some  years  ago  a  high 
degree  of  leucoderma  was  present.  In  two  of  my  cases  the  hair 
turned   rapidly  grey  during  the  development   of  the  anaemia  ;  in 

*  "Lancet,"  Vol.  I.,  1897,  p.  197. 


60  DISEASES   OF   THE   BLOOD. 

both  of  these  cases  the  colour  was  partly  regained  as  the  anaemia 
disappeared  under  the  administration  of  arsenic. 

Excessive  weakness,  languor  and  debility. — These  are  con- 
stant and,  on  the  whole,  perhaps,  the  most  prominent  symptoms  of 
the  disease  ;  they  are  often  the  first  symptoms  which  are  complained 
of;  towards  the  termination  of  the  case  the  debility  is  always  pro- 
found. Great  prostration  and  weakness  were  complained  of  in 
every  one  of  my  45  cases  (see  Table  3). 

The  general  state  of  nutrition. — In  most  cases  of  pernicious 
anaemia  emaciation  is  not  a  prominent  symptom,  though  excep- 
tions to  this  general  statement  are  occasionally  met  with.  The 
subcutaneous  fat  is  in  many  cases  well  preserved  ;  the  muscles  are 
usually  soft  and  flabby  and  more  or  less  (in  some  cases  consider- 
ably) wasted,  but  the  marked  emaciation  which  is  so  characteristic 
of  malignant  disease  is  rarely  present.  This  is  a  point  of  con- 
siderable diagnostic  importance,  for  in  some  cases  it  is  by  no  means 
an  easy  matter  to  distinguish  pernicious  anaemia  and  cancer  of  the 
stomach.  It  must,  however,  be  remembered  that  cases  are  some- 
times met  with  in  which  there  is  considerable  emaciation,  and  that 
in  most  cases  there  is  some  loss  of  weight. 

In  my  series  of  45  cases,  there  was  loss  of  weight  in  34  cases  ;  in 
1 5  of  these  34  cases,  the  loss  of  weight  was  slight,  in  the  remaining 
19  the  loss  was  more  or  less  considerable. 

The  skin  has  usually  a  soft  velvety  feel — another  point  of  dis- 
tinction between  pernicious  anaemia  and  most  cases  of  cancer  of 
the  stomach,  for  in  malignant  disease  the  skin  is  apt  to  become 
wrinkled  and  atrophied,  and  often  dry  and  harsh. 

In  some  cases,  but  in  my  experience  they  are  rare  (I  have  only 
met  one  well-marked  instance),  the  bones,  more  especially  the 
sternum  and  ribs,  are  tender  to  pressure  and,  it  may  be,  affected 
with  localised  swellings. 

The  condition  of  the  blood. — This  is  most  important.  Owing 
to  the  profoundly  bloodless  condition,  it  is  often  difficult  or 
impossible  by  simply  puncturing  the  finger  (puncturing  without 
bandaging),  to  obtain  a  sufficient  amount  of  blood  for  the  purposes 
of  accurate  examination.  A  prick  may  produce  little  or  no  bleed- 
ing. This  fact,  the  relatively  dry  condition  of  the  tissues,  and  the 
small  amount  of  blood  which  is  present  in  the  heart  and  blood 
vessels  after  death  seem  to  show  that  the  total  amount  of  blood  in 
the  body  is  reduced  in  quantity. 

When  a  drop  of  blood  is  obtained  by  simple  puncture  of  the 
finger,  or,  preferably,  by  puncturing  the  lobe  of  the  ear,  it  is  usually 
found  to  be  thin  and  watery-looking  ;  it  usually  looks  like  very  thin 


PERNICIOUS   AN/EMIA. 


61 


Table  3,  showing  the  more  important  Symptoms  in  45  Cases  of 

Pernicious  Anemia. 


Blood. 

i 

Sex. 

a 

Haemor- 

Urine. 

w 
u 

< 

Number  of 
Red 

■3 

Megalo- 

Micro- 

Poikilo- 

White 

T3 
C 

.c 
-J. 

rhages. 

> 

No. 

Corpuscles 

_o 

cytes. 

cytes. 

cytosis. 

Corpuscles. 

.2 

> 

b£ 

cj 

fa 

c 

M. 

F. 

(Lowest 

To 

'■y 

_: 

-i_ 

>> 

a. 
0 

P 

C 

8 

0 

.« 

++ 

Count). 

0 
B 
U 
X 

0 

0 

z 

- 

J3 
O 

£ 
0 
> 

J3 

P 

-a 
c 

CO 

1—) 

< 

3 

5 
O 

| 

<< 

1 

43 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

I 

?* 

O 

0 

0 

0 

0 

0 

N. 

T. 

2 

20 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

1 

0 

1 

Epis. 

1 

1 

1 

1 

1 

D. 

0 

3 

34 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Diminished 

1 

I 

1 

0 

1 

1 

0 

0 

I 

N. 

0 

4 

28 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Diminished 

1 

I 

1 

0 

1 

0 

1 

0 

0 

P. 

T. 

5 

29 

1 

1 

0 

1 

0 

0 

1 

1 

0 

P. 

0 

6 

38 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Diminished 

1 

I 

1 

0 

1 

1 

1 

0 

1 

P. 

0 

7 

31 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

No  excess 

1 

0 

1 

0 

x 

1 

1 

0 

0 

8 

47 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

No  excess 

1 

I 

1 

0 

1 

0 

1 

1 

0 

N. 

0 

9 

17 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Slight  excess 

1 

I 

0 

0 

1 

1 

0 

1 

0 

N. 

0 

10 

51 

1 

Much  dimd. 

Numerous 

Numerous- 

Moderate 

1 

0 

1 

0 

1 

1 

1 

0 

N. 

0 

11 

54 

1 

Mod.  dimd. 

Few 

Some 

Moderate 

No  excess 

1 

0 

0 

0 

1 

0 

0 

P. 

0 

12 

5° 

1 

1,470,000 

46% 

Numerous 

Numerous 

Marked 

1 

I 

0 

0 

0 

0 

1 

0 

N. 

T. 

13 

38 

1 

Much  dimd. 

Few 

Some 

Moderate 

No  excess 

1 

I 

Piles. 

0 

0 

x 

1 

D. 

T. 

14 

41 

1 

1 

I 

1 

Epis. 

0 

0 

0 

1 

1 

D. 

1 

15 

42 

1 

Much  dimd 

Numerous 

Numerous 

Marked 

1 

0 

1 

0 

1 

0 

0 

0 

1 

N. 

0 

16 

53 

1 

Much  dimd. 

Some 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

I 

0 

0 

T 

0 

0 

0 

N. 

0 

17 

54 

1 

1 

I 

1 

0 

T 

1 

t 

0 

N. 

0 

18 

62 

1 

1 

0 

0 

0 

O 

1 

1 

1 

N. 

T. 

19 

63 

1 

1,125,000 

35% 

Numerous 

Numerous 

Marked 

No  excess 

1 

I 

1 

0 

I 

1 

0 

1 

1 

D. 

0 

20 

53 

1 

Much  dimd. 

Some 

Numerous 

Marked 

No  excess 

1 

I 

9 

0 

I 

0 

0 

0 

D. 

T. 

21 

5i 

1 

900,000 

Marked 

1 

I 

I 

0 

I 

1 

0 

0 

0 

N. 

0 

22 

66 

1 

1 

I 

I 

0 

I 

1 

1 

1 

N. 

0 

23 

57 

1 

Much  dimd. 

Some 

Numerous 

Moderate 

No  excess 

1 

I 

I 

0 

O 

0 

1 

0 

1 

N. 

0 

24 

49 

1 

650  000 

20% 

Some 

Numerous 

Moderate 

4,000 

1 

I 

O 

Epis. 

O 

1 

1 

1 

1 

D. 

0 

25 

54 

1 

995,000 

28% 

Few 

Numerous 

Moderate 

1 

I 

O 

0 

O 

T 

1 

0 

I 

D. 

0 

26 

53 

1 

810,000 

20% 

Numerous 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

I 

I 

0 

I 

I 

0 

1 

I 

D. 

1 

27 

52 

1 

1,180,000 

33% 

Numerous 

Numerous 

Moderate 

Excess  of 
lymphocytes 

1 

I 

O 

Epis. 

O 

O 

0 

1 

0 

D. 

0 

28 

36 

1 

Much  dimd. 

Few 

Numerous 

Moderate 

Excess  of 
lymphocytes 

1 

0 

O 

0 

O 

I 

1 

1 

D. 

° 

29 

49 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

1 

I 

I 

0 

I 

I 

1 

N. 

0 

3° 

40 

1 

1 

I 

I 

0 

0 

O 

1 

0 

0 

N. 

0 

31 

16 

1 

450,000 

5% 

Some 

Some 

Moderate 

1 

I 

I 

Hjem. 

I 

I 

0 

0 

1 

D. 

0 

32 

42 

1 

Much  dimd. 

Few 

Numerous 

Marked 

No  excess 

1 

I 

I 

Hjeni. 

O 

I 

0 

0 

N. 

0 

33 

54 

1 

1,000,000 

Marked 

1 

0 

O 

0 

0 

O 

1 

1 

N. 

0 

34 

46 

1 

800,000 

18% 

Numerous 

Numerous 

Marked 

Diminished 

1 

I 

O 

0 

O 

O 

1 

0 

N. 

0 

35 

72 

1 

1 

I 

0 

0 

O 

I 

0 

0 

N. 

0 

36 

5° 

1 

1 

0 

0 

O 

I 

0 

1 

D. 

0 

37 

71 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

1 

I 

I 

0 

I 

I 

1 

1 

N. 

0 

38 

58 

1 

1 

I 

I 

0 

O 

I 

0 

1 

D. 

0 

39 

67 

1 

Much  dimd. 

Numerous 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

I 

I 

0 

I 

I 

1 

1 

N. 

0 

40 

37 

1 

816,000 

28% 

Some 

Numerous 

Moderate 

4.37" 

1 

I 

I 

0 

O 

I 

1 

1 

1 

D. 

0 

41 

5i 

1 

Much  dimd. 

. .    1  Numerous 

Numerous 

Marked 

1 

I 

I 

0 

I 

I 

1 

0 

N. 

0 

42 

3i 

1 

780,000 

29%!  Numerous 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

0 

I 

0 

I 

I 

0 

1 

1 

D. 

0 

43 

65 

1 

1,300,000 

32% 

Numerous 

Numerous 

Marked 

Excess  of 
lymphocytes 

1 

I 

I 

Epis. 

I 

I 

0 

1 

I 

N. 

T. 

44 

44 

1 

459,000 

14% 

Some 

Some 

Moderate 

Excess  of 
lymphocytes 

1 

I 

I 

0 

I 

0 

i 

I 

D. 

0 

45 

58 

1 

541,670 

20% 

Numerous 

Numerous 

Marked 

Excess  of 

1 

I 

0 

Piles. 

I 

0 

1 

1 

N. 

0 

! 

lymphocytes 

* 

n  this  case  retina  not  well  seen  owing  to  opacity  of  the  media.           t  Epis. 

=  E 

iistaxis.     Ha 

;m.  = 

=  H 

aem; 

itemesis. 

t  Is 

r.  =  Norma 

.     P.  =  Pal 

e.     D.  =  Da 

rk.             §  T 

=  T 

rac 

62  DISEASES   OF   THE   BLOOD. 

claret,  and  in  some  cases  immediately  separates  into  a  clear  watery 
part  and  a  more  deeply  stained  part.  In  some  cases  there  is  a 
tendency  of  the  puncture  to  continue  bleeding. 

In  order  to  obtain  a  drop  of  blood  of  sufficient  size  for  the 
purposes  of  accurate  examination,  it  is  usually  necessary,  after  mak- 
ing the  patient  hang  the  hand  down  over  the  side  of  the  bed  so  as 
to  allow  the  blood  to  gravitate  into  the  tips  of  the  fingers,  to 
bandage  one  of  the  fingers  tightly  from  the  meta-carpo-phalangeal 
joint  down  to  the  termination  with  a  strip  of  tape.  By  this  pro- 
cedure all  the  blood  which  is  contained  in  the  finger  is  pressed  into 
the  tip.  Owing  to  the  concentration  of  the  corpuscles,  the  drop  of 
blood  which  is  now  obtained  by  a  deep  puncture  is  more  deeply 
coloured,  and  the  number  of  red  blood  corpuscles  may,  when 
counted  in  the  ordinary  way,  appear  to  be  much  more  numerous, 
than  is  actually  the  case.  Hence  it  is  advisable  if  possible  to  avoid 
ligaturing  the  finger  and  to  estimate  both  the  haemoglobin  and  the 
red  blood  corpuscles  in  a  drop  of  blood  which  has  been  obtained  by 
simple  puncture.  As  I  have  just  stated  above,  a  drop  of  blood  can 
usually  be  obtained  without  any  difficulty  by  puncturing  the  lobe 
of  the  ear.  It  is  important  that  the  instrument  with  which  the 
puncture  is  made  should  be  perfectly  clean  and  very  sharp. 

The  most  striking  alteration  in  the  blood  is  the  diminution  in 
the  number  of  red  blood  corpuscles.  In  well-marked  cases  of 
pernicious  anaemia  the  red  blood  corpuscles,  instead  of  numbering 
5,000,000  (male)  or  4,500,000  (female)  per  cubic  millimetre,  are 
usually  found  to  be  reduced  to  less  than  1,500,000.  It  is  quite 
common  to  find  only  1,000,000  or  less.  In  several  of  the  recorded 
cases  only  500,000  red  corpuscles  were  present,  and  in  one  case 
described  by  Quincke  the  number  of  red  blood  corpuscles  only 
reached  143,000  ;  but,  as  Dr  Stephen  Mackenzie  has  pointed  out, 
Ouincke's  figures  always  read  low.  In  the  great  majority  of  cases 
in  which  the  red  blood  corpuscles  have  been  reduced  to  500,000 
per  cubic  millimetre,  the  patient  has  died  from  the  disease.  In 
Ouincke's  case  recovery  took  place. 

In  15  of  my  45  cases  blood  counts  are  recorded  ;  the  average 
corpuscular  richness  of  the  first  counts  in  these  15  cases  was 
1,250,384,  and  of  the  lowest  counts  829,600,  the  lowest  figure  being 
370,000  per  c.mm.  (see  Table  4).  In  52  cases  tabulated  by  Cabot, 
the  red  corpuscles  averaged  1,200,000  per  c.mm. 

In  the  advanced  stages  of  the  disease,  the  total  amount  of 
hemoglobin  is  always  greatly  reduced,  but  the  reduction  of  the 
haemoglobin  is,  in  most  cases,  relatively  less  than  that  of  the  red 
blood  corpuscles.  Consequently  the  individual  richness  of  the  red 
blood  corpuscles  in  haemoglobin  is  usually  equal  to  or  above  the 
normal.     In  a  case,  for  example,  which  I  had  under  my  observation 


PERNICIOUS   AN/EMI  A. 


63 


when  this  lecture  was  written,  the  red  blood  corpuscles  numbered 
1,125,000  per  c.mm.,  while  the  haemoglobin  (estimated  by  Gowers' 
instrument)  equalled  3 1  per  cent.  This  gives  the  following  for- 
mula : — JL=|i.,  instead  of  r\  =  t^,  which  represents  the  relative 
proportion  of  haemoglobin  to  red  corpuscles  as  estimated  in  health. 
But  since  Gowers'  instrument  reads  low  (85  per  cent,  to  90  per  cent, 
instead  of  100  per  cent,),  the  formula  should  really  be  SHC  =  -§f 
(instead  of  ft)  =  a  colour  index  1.4.  In  13  of  the  cases  included  in 
Table  3,  the  percentage  of  haemoglobin  was  estimated  ;  the  results 
are  set  forth  in  Table  4  ;  the  average  percentage  of  haemoglobin  in 
these  cases  when  the  patient  came  under  observation  (first  counts) 
was  30  per  cent,  and  the  average  colour  index  1.3. 


Table  4. — Condition  of  Blood  in  15  Cases  of 
Pernicious   Anaemia. 


No.  in 
Table  3. 

First  Count. 

Lowest  Count. 

Age. 

Sex. 

Number  of  Red 
Corpuscles. 

Haemo- 
globin. 

Colour 

Index 

corr'ct'd. 

NumberofRed 
Corpuscles. 

Haemo- 
globin. 

Colour 

Index 

corr'ct'd. 

12 

50 

M 

1,470,000 

Per  cent. 
46 

1-7 

1,470,000 

Per  cent. 
46 

17 

19 

63 

M 

1,250,000 

35 

i-5 

1,250,000 

35 

i-5 

21 

51 

M 

900,000 

24 

49 

M 

1,450,000 

46 

i-7 

650,000 

20 

17 

25 

54 

F 

995,000 

28 

i-4 

995,000 

28 

1.4 

26 

53 

M 

8lO,000 

20 

i-3 

8 1 0,000 

20 

i-3 

27 

52 

F 

1,400,000 

25 

.8 

1,1 18,000 

33 

i-5 

31 

16 

F 

900,000 

15 

.8 

450,000 

5 

•5 

33 

54 

M 

1,000,000 

34 

46 

M 

2,500,000 

30 

.6 

800,000 

18 

i-3 

40 

37 

M 

1,200,000 

44 

2. 

370,000 

16 

2.4 

42 

3i 

F 

780,000 

20 

1.4 

780,000 

20 

1.4 

43 

65 

F 

1,328,000 

32 

1.2 

1,050,000 

28 

i-3 

44 

44 

F 

I,l6o,000 

34 

1.4 

459,000 

14 

i-5 

45 

58 

M 

642,000 

16 

i-4 

542,090 

30 

2.2 

A^ 

/erage 

- 

1,250,384 

3° 

i-3 

829,000 

23 

i-5 

64  DISEASES   OF   THE   BLOOD. 

These  characters  of  the  blood  (the  marked  diminution  of  the  red 
corpuscles  and  the  fact  that  while  the  total  haemoglobin  is  greatly 
reduced  the  individual  corpuscular  richness  in  haemoglobin  is 
usually  equal  to,  and  often  greater  than,  the  normal)  are  of  the 
greatest  diagnostic  importance  ;  they  are  the  direct  opposite  of  the 
condition  of  the  blood  in  chlorosis  ;  and  they  differ  notably  from 
the  characters  of  the  blood  in  cases  of  secondary  anaemia  (anaemia 
due  to  loss  of  blood,  cancer  of  the  stomach,  etc.)  in  which  the 
blood  corpuscles  and  the  haemoglobin  are  (usually)  proportionately 
diminished.  I  will  return  to  this  point  when  I  come  to  speak  of  the 
diagnosis. 

In  estimating  the  individual  richness  of  the  corpuscles  in  haemo- 
globin it  must  be  remembered  that  in  pernicious  anaemia  a 
large  number  of  very  minute  red  corpuscles  (microcytes)  are 
almost  always  present.  Now  in  counting  the  red  corpuscles  the 
presence  of  these  very  minute  corpuscles  is  usually  ignored  ;  the 
smaller  microcytes,  at  all  events,  are  usually  omitted  from  the 
count.  It  is  obvious  that  there  is  a  source  of  fallacy  here.  If 
all  the  minute  corpuscles  are  included  in  the  count,  the  individual 
richness  of  the  red  blood  corpuscles  in  haemoglobin  (the  colour 
index)  will  in  many  cases  be  found  to  be  much  less  than  it  is 
usually  stated  to  be.  On  the  other  hand,  it  is  obvious  that  the  very 
small  microcytes  can  only  carry  a  very  minute  quantity  of  haemo- 
globin (though  the  amount  of  haemoglobin  which  they  contain 
may  be  larger,  in  proportion  to  their  relative  sizes,  than  that 
contained  by  the  megalocytes — this  is  strikingly  seen  in  the  case  of 
Eichhorst's  corpuscles) ;  and  since  the  blood  in  pernicious  anaemia 
usually  contains  large  numbers  of  megalocytes  which  ought  to  carry 
a  larger  quantity  of  haemoglobin  than  the  normally  sized  red 
corpuscles  (but  which  do  not  perhaps  always  do  so),  this  fallacy, 
due  to  counting  the  normally  sized  or  large  red  corpuscles  only,  is 
perhaps  more  apparent  than  real.  But  allowing  for  both  sources  of 
fallacy  (the  presence  of  microcytes  and  megalocytes),  there  can,  I 
think,  be  little  doubt  that  in  typical  cases  of  pernicious  anaemia  the 
individual  richness  of  the  corpuscles  in  haemoglobin  is  usually  above 
the  normal. 

In  my  15  cases  in  which  the  blood  was  counted,  the  haemoglobin 
was  also  estimated  in  13  ;  the  average  percentage  of  haemoglobin 
in  the  first  counts  was  (uncorrected)  30  per  cent.,  and  (corrected  for 
the  low  reading  of  Govvers'  instrument)  33  per  cent.,  and  the 
average  colour  index  (after  correction)  was  1.3,  the  highest  colour 
index  being  2.  and  the  lowest  .6  (see  Table  4). 

In  39  cases  of  pernicious  anaemia  observed  by  Cabot,  in  which 
the  red  cells  were  counted  and  the  haemoglobin  estimated,  the  red 
corpuscles  averaged  1,200,000  or  24  per  cent.,  while  the  haemoglobin 
averaged  26  per  cent.,  the  individual  corpuscular  richness  in  haemo- 


PERNICIOUS   AN/EMIA.  6$ 

globin  (the  colour  index)  being  consequently  (uncorrected)  1.08  and 
corrected  1.2  per  cent.* 

The  microscopical  alterations  which  the  red  blood  corpuscles 
present  are,  when  taken  in  connection  with  the  other  characters  of 
the  blood  (more  especially  the  number  of  red  corpuscles  and  the 
colour  index),  also  of  great  diagnostic  significance.  There  is  no 
disease  in  which  the  red  blood  corpuscles  are  so  markedly  altered 
in  size  and  shape  as  in  some  cases  of  pernicious  anaemia.  In  typical 
cases,  the  red  blood  corpuscles  do  not  go  into  rouleaux  ;  some  of 
them  are  larger  than  normal,  measuring,  it  may  be,  12/*.  or  even 
more  (jnegalocytes) ;  others  are  smaller  than  normal,  measuring  3/x. 
or  even  less  {inicrocytes).  Many  of  them  are  tailed,  horse-shoe- 
shaped,  pear-shaped,  battledore-shaped,  biscuit-shaped,  etc.  (poikilo- 
cytes). 

Apparently  active  amceboid  movements  can  not  unfrequently 
be  observed  in  the  irregular-shaped  red  corpuscles  ;  when  they 
occur  in  the  very  minute  red  corpuscles,  seen  sideways  on,  they 
may  closely  resemble  the  active  movements  of  bacteria.  For  the 
same  reason,  the  larger-sized  red  corpuscles,  when  seen  sideways, 
may  resemble  gigantic  bacteria.  Dr  Muir  tells  me  that  he  has 
never  seen  anything  to  suggest  that  the  red  corpuscles  in  pernicious 
anaemia  have  independent  movement ;  and  Dr  Gulland  informs  me 
that  in  his  opinion  the  movements  of  the  irregular  projections  of 
the  poikilocytes,  which  are  not  unlike  amceboid  movements  to  the 
eye,  are  due  to  physical  causes  and  not  to  actual  vital  movement. 
While  this  is  doubtless  correct,  the  movements  have  in  some  of  my 
cases  been  so  marked  that  I  was  at  one  time  disposed  to  think  that 
they  were  perhaps  vital. 

In  many  cases,  nucleated  red  blood  corpuscles  are  present, 
though  often  only  in  small  numbers. 

In  the  original  series  of  cases  of  pernicious  anaemia  which  came 
under  my  observation  in  the  year  1875,  I  minutely  described  the 
microscopical  characters  of  the  blood  and  published  an  illustrative 
plate.     My  description  was  as  follows  : — 

A  drop  of  blood  drawn  from  the  finger  in  the  usual  way  was 
found  to  be  thin  and  watery.  It  speedily  separated  into  two  parts,, 
one  coloured,  the  other  colourless,  looking  as  if  a  drop  of  colourless 
oil  had  been  added  to  a  red  liquid.  On  microscopical  examination 
it  presented  the  following  characters : — The  red  globules  were 
diminished  in  numbers,  and  did  not  form  rouleaux.  They  were 
markedly  altered  in  shape,  some  of  them  being  large,  and  no  longer 
biconcave ;  others  irregular,  and  with  one  or  more  tailed-like  pro- 

*  "Clinical  Examination  of  the  Blood,"  p.  122. 
E 


66  DISEASES   OF   THE   BLOOD. 

jections  ;  others  appeared  nucleated  ;  the  nucleus  was  of  a  pinkish- 
red  colour.  There  were  also  numerous  small  red  globules  ;  indeed, 
they  (the  red  globules)  seemed  to  be  of  all  sizes,  from  minute 
masses  of  protoplasm  to  the  abnormally  large  oval  corpuscles  which 
I  have  described.  (A  coloured  plate  illustrative  of  these  appear- 
ances was  published  with  the  original  paper.)  The  white  corpuscles 
were  not  increased.  In  addition  there  were  many  small  colourless 
granules  ;  some  of  these  formed  irregular  masses,  somewhat  larger 
than  white  blood  corpuscles.  In  one  specimen  an  emerald-green 
rod-shaped  body  about  TuVoth  of  an  inch  in  length  was  observed  ; 
it  seemed  to  move  with  a  slight  vibratile  movement.  Nothing  of 
the  sort  was  again  observed  ;  its  occurrence  was  therefore  probably 
accidental. 

In  the  drawing  which  illustrated  this  description  I  represented 
many  of  the  blood  corpuscles  as  nucleated.  I  now  know  that  the 
nucleated  appearance  was,  for  the  most  part,  apparent  only.  The 
appearances  which  I  supposed  were  indicative  of  a  nucleus  were 
shortly  afterwards  shown  by  Drs  Mackern  and  Davy  to  be  due  to 
a  concentration  of  the  haemoglobin  in  a  particular  part  of  the 
corpuscle.  This  apparent  nucleation  of  the  red  corpuscles  due  to 
concentration  of  the  haemoglobin  is,  in  my  experience,  invariably 
present  in  pernicious  anaemia.  Although  it  may  occur  in  a  slight 
degree  in  other  conditions,  I  am  disposed  to  think  that  it  is  an 
important  characteristic  of  the  disease. 

But  although  the  appearances  suggestive  of  nucleation  of  the 
red  corpuscles  are  in  unstained  preparations  usually  due  to  con- 
centration of  the  haemoglobin  in  a  particular  part  of  the  corpuscle, 
it  is  certain  that  in  the  great  majority  of  cases  of  pernicious  anaemia, 
nucleated  red  blood  corpuscles  are  actually  present ;  they  can  only 
be  satisfactorily  seen  in  stained  preparations. 

Some  of  the  red  blood  corpuscles — and  this  statement  more 
particularly  applies  to  the  unusually  large  corpuscles  (megalo- 
cytes) — contain  little  or  no  colouring  matter  {shadow-corpuscles)  ; 
others  are  uncoloured  in  their  centres  (apparent  vacuolation) ;  others 
appear  to  be  really  vacuolated. 

Deeply  stained  microcytes,  which  were  first  described  by 
Eichhorst  and  are  consequently  termed  "  Eichhorsfs  corpuscles," 
are  sometimes  present,  though  in  my  experience  much  less 
frequently  than  some  observers  seem  to  indicate — indeed,  I  have 
seen  them  in  only  two  or  three  cases.  When  present,  they  are  of 
considerable  diagnostic  importance. 

Several  different  observers  have  claimed  to  have  seen  organisms 
in  the  blood  of  pernicious  amemia ;  in  more  than  one  case  of  the 
disease,    flagellated    organisms  have    been    described.      In    several 


PERNICIOUS   ANAEMIA.  67 

cases  which  have  come  under  my  own  notice,  I  have  seen  appear- 
ances which  seemed  to  me  suggestive  of  organisms  ;  and  in  one 
case,  observed  some  years  ago,  I  made  a  series  of  cultivations  from 
the  blood,  and  a  very  definite  growth  was  obtained  in  gelatine. 
Dr  Arthur  Hare  examined  the  cultivations  for  me  and  stated  that 
they  consisted  of  a  short  thick  bacillus  with  rounded  sides  which 
was  growing  very  rapidly.  He  further  stated  : — "I  cannot  recognise 
it"  (the  bacillus)  "as  any  with  which  I  am  acquainted,  but  from  its 
character  and  rapidity  of  growth  I  am  inclined  to  think  it 
saprophytic."  The  presence  of  this  organism  was  probably  acci- 
dental ;  for  in  three  recent  cases  in  which  the  disease  was  extremely 
well  marked,  Dr  Robert  Muir  failed  to  detect  any  organisms  in  the 
blood  either  in  stained  films  or  in  gelatine  tubes  after  incubation. 
As  I  have  already  stated,  the  apparently  actively  moving  minute 
microcytes,  if  seen  sideways  on,  are  very  apt  to  be  mistaken  for 
micro-organisms. 

In  uncomplicated  cases  of  pernicious  anaemia,  the  white  blood 
corpuscles  are  almost  always  diminished,  sometimes  markedly  so  ; 
though  after  haemorrhage,  or  with  any  inflammatory  complication 
there  may  be  a  considerable  leucocytosis. 

The  percentage  of  lymphocytes  is  usually  much  increased,  while 
the  polymorphonuclear  oxyphiles  (or  neutrophils)  are  diminished. 
Eosinophils  are  sometimes  increased,  and  myelocytes  are  occa- 
sionally present  in  small  numbers.  As  the  disease  approaches  its 
termination,  the  number  of  leucocytes  is  usually  still  further 
diminished. 

The  blood-plates  are  usually  diminished  in  number,  sometimes 
markedly  so.  The  fibrin  network  usually  forms  less  quickly  and  is 
less  dense  than  under  normal  circumstances,  consequently  the  blood 
usually  coagulates  less  quickly  than  normal. 

The  haemoglobin  stability  is  markedly  impaired.  I  have 
already  pointed  out  that  the  haemoglobin  tends  to  become  con- 
centrated in  a  particular  part  of  the  corpuscle  and  to  give  an 
appearance  of  apparent  nucleation.  Dr  Copeman  has  also  shown 
that  the  haemoglobin  tends  to  separate  readily  out  of  the  corpuscles 
when  the  blood  is  removed  from  the  body.  This  instability  of  the 
haemoglobin  appears  to  be  of  importance  in  connection  with  the 
pathology  of  the  disease. 

The  specific  gravity  of  the  blood  is  diminished. 

Cabot  sums  up  the  characters  of  the  blood  in  pernicious  anaemia 
as  follows  : — 

"  1.  Red  cells  about  1,000,000  per  cubic  millimetre. 

2.    White  cells  much  diminished. 


68  DISEASES   OF   THE   BLOOD. 

3.  Haemoglobin  variable,  sometimes"  (I  would  say  in  the  great 

majority    of   cases)    "increased   relatively    (  =  high-colour 
index). 

4.  Deformities  in  size  and  shape  of  red  cells  in  many"  (I  would 

say  in  almost  all  well-marked)  "  cases. 

5.  Increase  in  average  diameter  of  red  cells."      (I    do   not   feel 

satisfied  as  to  this,  if  the  microcytes  are  included,  as  they 

ought  to  be,  in  the  calculation.) 
"  6.  Polychromatophilic  red  cells. 
7.  Megaloblasts  more  numerous  than  normoblasts"     (I  have  not 

always  observed  this.) 
"  8.  Lymphocytosis. 

9.  Small  percentage  of  myelocytes. 

The    items    italicised    are    the    most    important    and    charac- 
teristic."* 

To  these  characters  I  would  add  : — 

10.  Marked  defect  in  rouleaux  formation. 

11.  Marked  tendency  for  the  haemoglobin  to  be  concentrated  in 

localised  parts  of  the  red  corpuscles,  giving  an  appearance 
of  apparent  nucleation. 

12.  The  presence  in  many  cases  of  truly  nucleated  red  corpuscles. 

13.  Diminished  stability  of  the  haemoglobin. 

14.  Great  frequency,  in  well-marked  cases,  of  microcytes,  often 

of  very  minute  size — from  mere  points  up  to  the  average- 
sized  red  corpuscles. 

15.  The  occasional  presence  of  deeply-stained  microcytes  (Eich- 

horst's  corpuscles). 

16.  Blood-plates   usually  diminished  in    number  and    in    some 

cases  markedly   so  ;  and  the  fibrin  network  less  quickly 

formed  and  less  dense  than  normal. 
Such,  then,  are  the  most  important  microscopic  changes  in  the 
blood.  Though  highly  significant  and  characteristic,  it  is  perhaps 
premature  to  conclude  that  these  changes  are  absolutely  pathog- 
nomonic of  a  single  definite  disease  —  a  single  clinical  entity. 
What  I  mean  to  say  is,  that  it  has  not  yet  been  definitely  shown  that 
the  same  changes  may  not  occur  in  other  conditions  in  which  the 
red  blood  corpuscles  are  for  a  long  time  profoundly  reduced  in 
number  (as  from  a  long-continued  drain  of  blood)  and  in  which  the 
red-blood-forming  organs  (the  marrow  of  the  bones)  are  for  long 
periods  of  time  called  upon  to  rapidly  produce  an  excessive  number 
of  red  blood  cells — in  other  words,  in  cases  in  which,  as  the  result 

*  "Clinical  Examination  of  the  Blood,"  p.  128. 


PERNICIOUS   ANAEMIA.  69 

of  a  long-continued  and  excessive  strain  on  the  blood-forming 
organs,  the  production  is  too  rapid  and  consequently  defective,  i.e., 
in  cases  in  which  many  immature  and  imperfectly-formed  red  blood 
corpuscles  are  thrown  into  the  circulation. 

The  condition  of  the  heart  and  pulse. — -Palpitation  and  short- 
ness of  breath  on  exertion  are  constant  symptoms.  Praecordial 
pain  is  occasionally  complained  of,  but  a  more  frequent  symptom 
is  a  feeling  of  sinking  or  "goneness"  in  the  region  of  the  stomach 
(epigastric  region).  Giddiness,  fainting  and  tinnitus  aurium  are 
very  common.  As  I  have  already  remarked,  in  well-marked  cases 
of  pernicious  anaemia  the  cardiac  cavities  are  usually  dilated  and 
the  heart  muscle  is  in  the  great  majority  of  instances  found  after 
death  to  be  in  an  advanced  state  of  fatty  degeneration  ;  in  fact, 
if  I  may  judge  from  my  own  pathological  experience,  there  is  no 
disease  in  which  fatty  degeneration  of  the  heart  is  so  marked  as  in 
pernicious  anaemia.  As  in  chlorosis,  the  heart  muscle,  which  is 
affected  in  this  way  is  not  only  weak  but  abnormally  irritable. 
Quite  exceptionally,  in  severe  and  long  continued  cases  of  the 
disease,  the  heart  muscle  is  not  fatty  ;  a  striking  illustration  came 
under  my  notice  quite  recently  (Case  45). 

The  cardiac  impulse  is  usually  diffused,  the  praecordial  dulness 
(unless,  as  is  not  unfrequently  the  case,  the  lungs  should  be  emphy- 
sematous) usually  increased. 

The  pulse  is  usually  quicker  than  normal  ;  sometimes  large,  but 
more  frequently  small ;  soft,  of  low  tension  and  often  dicrotic  in 
character  ;  in  the  advanced  stages  of  the  disease  the  pulse  may  be 
jerking  in  character ;  the  jerking  collapsing  character  is  in  some 
cases  so  marked  as  to  suggest  the  presence  of  aortic  regurgitation. 
Trivial  excitements  are  apt  to  increase  the  frequency  of  the  pulse 
and  to  produce  palpitation. 

A  venous  hum  can  almost  always  be  heard  in  the  neck.  In  the 
advanced  stages  of  the  disease,  the  external  jugular  veins  are  often 
knotted  and  distended,  or  the  seat  of  true  venous  pulsation  indi- 
cative of  tricuspid  regurgitation. 

A  systolic  murmur  is  generally  present  in  the  pulmonary 
area  ;  in  many  cases  a  systolic  murmur  may  also  be  heard  in  the 
mitral,  tricuspid  and,  less  frequently,  in  the  aortic  areas.  The 
cardiac  impulse  while  at  rest  and  unexcited  is  diffused,  feeble, 
flickering  and  the  transverse  dulness  in  particular  increased.  In 
many  cases,  the  lungs  are  emphysematous  and  the  increased  area  of 
cardiac  dulness  is  consequently  less  marked  than  one  would  expect 
from  the  appearance  of  the  heart  after  death.  The  condition  of 
the   heart  is,  in  short,  similar  to  that  which  is  met  with  in  aggra- 


JO  DISEASES   OF   THE    BLOOD. 

vated  and  long-continued  cases  of  chlorosis  ;  but  in  the  advanced 
stages  of  pernicious  anaemia  the  cardiac  alterations  are  much  more 
marked  and  the  heart  symptoms  usually  more  prominent  than  in 
the  most  severe  cases  of  chlorosis. 

Retinal  and  other  haemorrhages. — In  the  majority  of  well- 
marked  cases  of  the  disease,  hemorrhages  are  present  in  the 
retina.  In  my  45  cases,  retinal  haemorrhages  were  present  in  28  ; 
there  were  no  retinal  haemorrhages  in  12  ;  and  in  the  remaining  5 
cases  the  presence  or  absence  of  retinal  haemorrhages  is  not  men- 
tioned in  the  notes,  or  the  fundus  was  not  examined  or  could  not 
be  examined  owing  to  opacities  of  the  media.  The  presence  of 
retinal  haemorrhages  is  consequently  of  considerable  diagnostic 
importance. 

The  haemorrhages  are  usually  of  small  size,  scattered  here  and 
there  over  the  retina.  In  some  cases  larger  haemorrhages  are  seen, 
usually  in  the  course  of  the  larger  vessels.  Striated  flame-like 
haemorrhages  extending  out  from  the  margin  of  the  disc  are  not, 
however,  uncommon.  In  some  cases,  the  central  part  of  the 
haemorrhage  is  paler  than  the  circumference  ;  it  may  be  of  a  pale 
yellow  colour  or  almost  white.  In  exceptional  cases,  there  is  some 
swelling  and  inflammation  of  the  optic  discs  (papillitis).  Further,  I 
may  here  state  that  in  well-marked  cases  of  the  disease  the  pallor 
of  the  fundus  oculi  is  very  striking. 

Other  hcemorrhages. — According  to  most  authorities,  haemor- 
rhages (other  than  retinal  haemorrhages)  are  common  in  the 
advanced  stages  of  pernicious  anaemia,  but  in  the  cases  which  have 
come  under  my  own  notice  they  were  rare.  Epistaxis,  haemate- 
mesis,  and  bleeding  from  the  throat  and  gums  are  the  most  frequent. 
Bleeding  from  the  bowel,  uterus  and  vagina  occasionally  occurs. 
In  the  advanced  stages  of  the  disease,  petechial  haemorrhages  are 
sometimes  found  in  the  skin,  more  particularly  on  the  lower 
extremities.  In  one  of  my  cases  in  which  there  were  no  haemor- 
rhages, the  skin  bruised  very  readily,  slight  injuries  producing 
extensive  subcutaneous  extravasations. 

In  my  series  of  45  cases,  epistaxis  occurred  in  5  cases,  haema- 
temesis  in  2  cases,  and  in  2  there  was  bleeding  from  piles. 

As  I  shall  point  out  when  I  come  to  describe  the  post-mortem 
appearances,  hemorrhages  beneath  the  pericardium,  the  pleura,  the 
peritoneum  and  into  the  delicate  tissue  of  the  brain  are  very  gene- 
rally present  in  the  bodies  of  patients  who  have  died  from  the 
disease.  I  am  strongly  of  opinion  that  these  petechial  hemorrhages 
are  the  result,  not  the  cause,  of  the  disease;  there  can  I  think  be 
little  doubt  that  they  are  due  to  the  structural  (fatty)  changes  which 


PERNICIOUS   ANEMIA.  71 

are  apt  to  be  produced  in  the  walls  of  the  minute  blood  vessels  in  all 
cases  of  profound  and  long-continued  anaemia  in  which  the  red 
blood  corpuscles  are  greatly  reduced  in  number. 

I  may  take  this  opportunity  of  saying  that  in  cases  of  anaemia 
the  occurrence  of  haemorrhages  seems  to  depend  chiefly  upon  the 
number  of  red  blood  corpuscles  which  are  present  and  the  dura- 
tion of  the  anaemia.  Whenever  the  red  blood  corpuscles  are  for 
any  length  of  time  greatly  reduced  in  number,  retinal  and  other 
haemorrhages  are  apt  to  occur. 

Febrile  attacks. — During  the  course  of  pernicious  anaemia 
temporary  attacks  of  pyrexia  are  of  frequent  occurrence  and  of 
considerable  diagnostic  value. 

In  some  cases,  the  fever  is  continuous  ;  in  others — and  this  is 
more  common— -intermittent  or  remittent.  The  fever  has  been 
termed  "  amzmic  fever  "  or  "  the  essential  fever  of  ancemia."  In 
many  cases,  the  febrile  attacks  seem  to  be  associated  with  a  rapid 
destruction  of  red  blood  corpuscles,  which  is  apt  to  occur  from  time 
to  time  in  what  may  be  termed  a  paroxysmal  manner.  During 
these  paroxysms  there  is  usually  an  exacerbation  of  the  symptoms, 
the  urine  often  becomes  deeply  pigmented,  the  patient  may  become 
jaundiced,  and,  as  has  just  been  stated,  fever  maybe  developed.  In 
many  cases  in  which  little  or  no  febrile  disturbance  is  noticed 
during  the  course  of  the  disease,  the  temperature  runs  up,  sometimes 
to  a  high  point,  just  before  death.  In  a  few  cases  recurring  attacks 
of  chilliness  or  actual  rigors  occur. 

In  my  series  of  45  cases,  irregular  attacks  of  fever  were  noted 
in  17  cases  ;  in  7  cases  it  is  definitely  stated  in  my  notes  that  there 
was  no  fever  ;  in  the  remaining  21  cases  the  presence  or  absence  of 
fever  was  not  ascertained  or  was  not  noted  ;  many  of  these  cases 
were  seen  only  once  in  consultation. 

The  exact  cause  of  the  febrile  attacks  which  so  frequently 
occur  during  the  course  of  pernicious  anaemia  has  not,  so  far  as  I 
am  aware,  been  definitely  determined.  As  I  have  just  stated  the 
febrile  paroxysms  seem  to  occur  in  association  with  paroxysmal 
exacerbations  of  blood  destruction.  The  fever,  like  the  blood 
destruction,  is  perhaps  the  result  of  the  presence  of  a  poison  (a 
toxin  or  ptomaine)  in  the  blood,  it  may  be  the  same  poison 
which  produces  the  blood  destruction,  or  possibly  of  some  fever- 
producing  substance  developed  during  the  process  of  blood 
destruction. 

The  condition  of  the  urine. — In  the  majority  of  the  cases  of  per- 
nicious anaemia  which  have  come  under  my  own  notice  the  urine  has 
presented  no  abnormal  appearance  ;  as  a  rule,  it  has  been  normal  in 


72  DISEASES   OF   THE   BLOOD. 

colour  or  paler  than  normal.  During  the  paroxysmal  exacerbations 
and  in  the  advanced  stages  of  the  disease  it  may,  as  I  have  already 
mentioned,  be  more  deeply  coloured  than  normal.  In  some  cases, 
at  all  events,  this  excessive  pigmentation  appears  to  be  due  to  the 
presence  of  pathological  urobilin.  Dr  William  Hunter  and  Dr 
Mott  think  that  the  deep  pigmentation  of  the  urine  is  an  important 
clinical  indication  of  the  excessive  blood  destruction  which  is  taking 
place.  When  the  blood  destruction  is  excessive,  part  of  the  pigment 
is  excreted  by  the  kidneys  ;  and  after  death  microscopical  deposits 
of  pigment,  which  give  the  iron  reaction  with  hydrochloric  acid 
and  ferrocyanide  of  potassium,  have  been  found  in  the  renal  tubules. 
Dr  Hunter  states  that  in  some  cases  in  which  the  urine  is  deeply 
coloured,  not  only  is  pathological  urobilin  present  in  the  urine  in 
large  quantities,  but  the  presence  of  blood  pigment  may  be  recog- 
nised in  the  urine  in  the  form  of  microscopical  granules  and  on 
analysis  the  iron  excreted  in  the  urine  is  increased  in  amount.  In 
some  cases  the  urine  contains  an  excess  of  indican. 

In  my  series  of  45  cases,  the  urine  was  normal  in  colour  in  23  ; 
dark  in  16  ;  and  pale  in  5  ;  in  one  case  the  colour  of  the  urine  is  not 
noted.  There  can,  however,  be  little  doubt  that  if  the  condition  of 
the  urine  had  been  carefully  observed  throughout  the  course  of  the 
28  cases  in  which  it  is  noted  as  normal  or  pale,  deep  pigmentation 
would  have  been  observed  in  many,  perhaps  in  all  of  them,  at  some 
period  or  other  of  their  course. 

In  some  cases,  the  urine  deposits  large  quantities  of  uric  acid  ; 
a  very  striking  case  of  this  kind  came  under  my  observation  some 
years  ago  ;  the  same  condition  was  present  in  the  deeply  jaundiced 
case  to  which  I  have  already  referred. 

In  some  cases  the  urine  contains  albumen  ;  it  is  usually  small  in 
amount  and  unattended  with  tube  casts  ;  in  most  cases  it  is  merely 
temporary ;  in  some  cases  it  disappears  with  the  improvement 
which  in  many  cases  results  from  arsenical  treatment.  In  my  series 
of  45  cases  albumen  was  present  in  9  cases  ;  in  7  of  these  only  in 
small  quantity  (a  trace)  ;  in  36  cases  there  was  no  albumen  ;  and  in 
the  remaining  10  cases  the  presence  or  absence  of  albumen  is  not 
mentioned  in  the  notes. 

In  some  cases  the  combined  sulphates  are  in  marked  excess. 

The  condition  of  the  respiratory  system. — Shortness  of  breath 
on  exertion  is  always  present  even  in  the  earlier  stages  of  the 
disease.  In  the  later  stages,  attacks  of  shortness  of  breath  may  occur 
independently  of  effort  (anaemic  dyspnoea).  Cough  (unless  a  nervous 
cough)  is  not  usually  observed  except  as  the  result  of  some  compli- 
cation ^pneumonia,  bronchitis,  oedema  of  the  lungs,  hydrothorax). 


PERNICIOUS   AN.EMIA.  73 

All  of  these  conditions  are  rare,  though  in  my  experience  pneumonia 
is  sometimes,  and  cedema  of  the  lungs  frequently  a  cause  of  death. 

The  condition  of  the  digestive  system. — Symptoms  indicative 
of  functional  derangement  of  the  stomach  and  intestines  are  almost 
invariably  present. 

Anorexia  is  usually  a  prominent  symptom  (in  one  of  my  cases  the 
appetite  was  excessive) ;  flatulent  dyspepsia  is  common  ;  nausea 
and  vomiting  are  of  frequent  occurrence  ;  in  some  cases  the  vomiting 
occurs  in  paroxysms. 

In  my  series  of  45  cases,  vomiting  was  present  (though  in  many 
of  these  cases  only  as  an  occasional  and  slight  symptom)  in  31; 
there  was  no  vomiting  in  14  cases. 

In  at  least  half  of  the  cases  there  is  diarrhoea  ;  in  other  cases  the 
bowels  are  normal  ;  in  a  small  proportion  of  cases  constipated.  In 
my  45  cases,  diarrhoea  occurred  in  24  cases  ;  in  many  of  these  the 
diarrhoea  was  very  troublesome.  I  may  further  say  that  in  some 
of  the  cases  which  have  come  under  my  notice,  the  development  of 
the  disease  has  been  preceded  by  intractable  diarrhoea  ;  and  in 
more  than  one  of  these  cases  I  have  found  the  intestines  ulcerated 
after  death.  I  am  disposed  to  think  that  prolonged  diarrhoea  is  in 
some  cases  an  important  factor  in  the  production  of  the  disease ; 
though,  in  cases  of  this  kind,  the  diarrhoea  and  the  pernicious 
anaemia  may  of  course  be  due  to  a  common  cause — the  presence 
of  some  organism  or  other  irritant  in  the  intestine. 

These  conclusions  as  to  the  frequency  of  vomiting  and  diarrhoea 
are  quite  in  accord  with  the  observations  of  Dr  Hale  White  ;  he 
states,  "  We  may  therefore  conclude  that  dyspeptic  symptoms,  par- 
ticularly vomiting  and  diarrhoea,  are  very  common  in  genuine 
pernicious  anaemia,  being  present  in  almost  half  the  cases,  that  they 
are  often  very  severe,  and  that  constipation  is  one  of  the  least 
common  of  the  dyspeptic  symptoms."  * 

The  tongue  is  usually  very  pale  ;  in  many  cases,  it  is  remark- 
ably smooth,  apparently  destitute  of  its  surface  epithelium,  but  rarely 
raw-looking ;  I  attach  considerable  diagnostic  significance  to  this 
condition  of  the  tongue  ;  it  has  been  a  notable  feature  in  many  of 
my  cases.  In  other  cases,  the  tongue  is  flabby  and  indented  by  the 
teeth  ;  in  some  cases  it  is  furred  ;  in  the  later  stages  of  the  disease 
it  is  frequently  dry.  In  two  or  three  of  my  cases  an  ulcerated  or 
inflamed  condition  of  the  gums  has  been  present ;  in  one  case  this 
condition  of  the  gums  and  buccal  mucous  membrane,  which  was 


Guy's  Hospital  Reports,  Vol.  47,  1890. 


74  DISEASES   OF   THE   BLOOD. 

perhaps  an  indication  of  a  similar  condition  in  the  whole  gastro- 
intestinal tract,  preceded  the  development  of  the  pernicious  anaemia. 
During  the  later  stages  of  the  disease — and  sometimes  in  the 
earlier  stages — the  patient  often  suffers  from  distressing  thirst. 

On  physical  examination,  the  stomach  is  in  some  cases  found  to 
be  dilated  ;  the  free  hydrochloric  acid  in  the  gastric  juice  is,  it  is 
said,  in  most  cases  much  diminished  in  amount,  or  it  may  be 
entirely  absent. 

In  some  cases  the  faeces  contain  parasitic  organisms  or  their  ova  ; 
hence  in  all  cases  of  pernicious  anaemia  a  careful  microscopic 
examination  of  the  faeces  should  be  made.  In  all  of  my  recent 
cases  the  stools  have  been  carefully  examined  for  parasites  ;  but  in 
no  case  have  parasites  been  found. 

The  condition  of  the  nervous  system. — Giddiness  on  rising 
from  the  recumbent  to  the  erect  position  and  on  stooping,  fainting 
on  slight  exertion  or  after  a  free  evacuation  of  the  bowels,  tinnitus 
aurium,  buzzing  and  throbbing  sensations  in  the  head  and  headache 
are  very  common  symptoms.  The  temper  is  in  many  cases  unduly 
irritable.  The  patient  is  unable  to  carry  out  any  sustained  mental 
effort ;  he  easily  becomes  exhausted  and  tired.  The  memory  is  in 
some  cases  impaired.  In  many  cases  the  patient  complains  of  dim- 
ness of  vision,  of  black  specks  floating  before  the  eyes  ;  these 
symptoms  are  especially  marked  in  those  cases  in  which  the  retinal 
haemorrhages  are  numerous,  and  in  the  cases  in  which  the  optic 
discs  are  swollen  and  inflamed.  In  some  cases  there  is  slight 
deafness. 

Symptoms  indicative  of  derangement  of  the  functions  of  the 
spinal  cord  are  met  with  in  a  certain  proportion  of  cases  and  are 
readily  explained  by  the  very  marked  and  definite  lesions  in  the 
cord  (usually  sclerotic  changes  in  the  posterior  and  lateral  columns) 
which  in  some  cases  have  been  found  after  death.  These  symptoms 
chiefly  consist  of  numbness  or  tingling  in  the  toes,  feet,  legs,  fingers 
and  hands  ;  muscular  weakness,  especially  in  the  lower  extremities  ; 
and  inco-ordination.  In  some  cases  there  are  shooting  pains,  re- 
sembling the  lightning  pains  of  locomotor  ataxia  ;  in  other  cases 
there  is  rigidity  and  spasticity;  in  rarer  cases,  marked  and  localised 
muscular  atrophy.  In  some  cases  the  knee-jerks  are  exaggerated, 
in  others  abolished.  The  functions  of  the  bladder  and  rectum  are 
rarely  deranged,  except  in  the  later  stages  of  those  cases  in  which 
the  spinal  lesions  are  extensive  and  advanced. 

Lichtheim  was  the  first  to  direct  attention  to  these  cord  changes. 
Minnich,  Xonne,  James  Taylor,  Risien  Russell  and  several  other 
physicians  have  published  important  observations  on  the  subject. 


PERNICIOUS   AN/EMIA.  75 

The  cord  lesions  are  admirably  illustrated  and  a  complete  resume 
of  the  literature  up  to  date  is  given  in  Taylor's  communication  * 
and  in  Risien  Russell's  paper,  f 

In  the  advanced  stages  of  the  disease,  sleeplessness  and  an 
extremely  distressing  and  painful  condition  of  uneasiness  and  rest- 
lessness are  often  present.  Finally,  the  patient  may  pass  into  a 
drowsy  semi-comatose  condition  ;  in  other  cases,  delirium,  epilepti- 
form convulsions  or  profound  coma  occur.  It  is  needless  to  say 
that  these  symptoms  are  usually  the  precursors  of  death. 

The  frequency  of  occurrence  of  some  of  the  more  important 
symptoms  in  my  45  cases  of  pernicious  anaemia  is  shown  in  Table  3. 

Etiology. 

Age. — Pernicious  anaemia  usually  occurs  in  adults,  most  fre- 
quently if  I  may  judge  from  my  own  experience  between  the  ages 
of  35  and  55. 

In  the  45  cases  which  I  have  personally  observed,  2J  occurred 
between  the  ages  of  35  and  54  inclusive  ;  8  cases  occurred  below 
the  age  of  35,  and  10  cases  above  the  age  of  54.  The  number  of 
cases  occurring  in  each  of  the  five  years  between  1 5  and  74  in  my 
series  of  cases  is  shown  in  the  following  table  : — 

Table  5.— Showing  the  Age  Distribution  in  45  Cases  of 
Pernicious  Anaemia. 


Years 

15  to 

19 

20   „ 

24 

25    ,, 

29 

SO    „ 

34 

35  » 

39 

4o  „ 

44 

45  „ 

49 

Cases. 


Years.  Cases. 

5Ot0  54  -            -  -  -  13 

55  »  59  -        -  -  -  3 

60  ,,  64                -  -  -  2 

65  „  69                -  -  -  3 

70  „  74  -        -  -  -  2 

Total  -  -  45 


I  do  not  wish  to  attach  too  much  importance  to  these  figures,  for 
the  total  number  of  cases  is  too  small  to  allow  of  a  definite  conclu- 
sion, and  my  results  are  not  in  accord  with  the  statistics  of  some 
other  observers.  Thus,  in  103  cases  collected  by  Pye-Smith^  from 
various  sources  the  average  age  was  thirty-four  years  and  four 
months  ;  and  in  36  American  cases  collected  by  Musser  §  19 
occurred  below  the  age  of  40. 

*  Medico-Chirurgical  Transactions,  Vol.  78,  1895. 
t  "  Lancet,"  1898,  2nd  July,  p.  4. 
t  Guy's  Hospital  Reports,  Vol.  xxvi. 

§  On  Idiopathic  Anaemia,  by  Dr  J.  H.  Musser,  Proceedings  of  the  Phila- 
delphia County  Medical  Society,  1885. 


j6  DISEASES   OF   THE   BLOOD. 

Sex. — The  statements  of  different  observers  differ  as  to  the 
frequency  with  which  the  two  sexes  are  liable  to  be  affected  ;  in 
some  of  the  lists  of  cases  which  have  been  published,  females  were 
more  frequently  affected  than  males.  In  my  45  cases,  29  of  the 
patients  were  males  and  16  females. 

Distribution. — The  disease  seems  to  occur  in  all  countries  and 
in  persons  of  all  occupations.  From  the  observations  of  Biermer 
and  Immermann  it  would  seem  to  be  specially  common  in  Switzer- 
land ;  but  as  Dr  Gulland  has  pointed  out  to  me  this  great  frequency 
in  Switzerland  may  perhaps  be  due  to  the  fact  that  cases  of 
anaemia  due  to  the  ankylostoma  duodenale  (which  appear  to  be 
unusually  frequent  in  Switzerland)  are  included. 

Rank  in  life. — About  half  of  the  cases  which  have  come  under 
my  own  notice  have  occurred  in  fairly  well-to-do  or  well-to-do 
people,  but  it  is  probable  I  think  that  the  disease  is  more  common 
amongst  the  lower  orders  of  society  and  amongst  those  whose  diet, 
social  habits  and  sanitary  surroundings  are  unsatisfactory. 

Influence  of  heredity. — So  far  as  I  know,  a  hereditary  ten- 
dency to  pernicious  anaemia  can  very  rarely  be  traced  ;  indeed  the 
only  instance  with  which  I  am  acquainted  in  which  the  disease 
appeared  to  be  inherited  occurred  in  the  practice  of  Dr  Allison  of 
Kettering.  The  patient,  a  man  aged  53,  was  under  Dr  Allison's 
care  with  all  the  typical  symptoms  of  pernicious  anaemia  and  died 
from  the  disease.  Dr  Allison  writes  me : — "  I  venture  to  think 
that  in  this  case  there  is  a  distinct  hereditary  taint.  His  mother 
died  here  aged  60,  certified  cardiac  weakness  and  chronic  diarrhoea; 
before  she  died  she  consulted  Dr  Francis,  one  of  the  physicians  to 
the  Northampton  Infirmary,  who  said  that  she  had  a  peculiar 
disease  of  the  blood  which  would  probably  be  fatal.  One  aunt 
died  at  Mansfield  in  1879,  aged  55,  the  certificate  gave  the  cause 
of  death  anaemia.  Another  aunt  died  at  Croydon,  aged  46,  of 
morbus  cordis.  An  uncle  died  at  Kettering  in  1885,  aged  51, 
certificate  congestion  of  the  liver;  his  widow  tells  me  that  he 
suffered  a  good  deal  from  vomiting  and  feverish  attacks  during  the 
last  year  of  his  life  and  that  he  looked  exactly  like  his  nephew  is 
at  present  (typical  and  advanced  pernicious  anaemia).  An  uncle 
died  this  year  (February)  at  Wakefield,  aged  74  ;  the  cause  of 
death  was  certified  by  Dr  Eddison  of  Leeds  as  pernicious  anaemia. 
The  patient  has  a  brother,  aged  51,  at  Willesden  very  ill  just  now, 
like  himself  in  symptoms,  I  am  told." 

Other  exciting  or  predisposing  causes. — In  many  of  the 
reported  cases  the  patients  have,  up  to  the  onset  of  the  disease, 
enjoyed  good  health.     In  a  considerable  proportion  of  cases,  the 


PERNICIOUS   AN/EMIA.  77 

disease  is  preceded  by  dyspeptic  troubles  or  diarrhoea.  In  some 
cases  the  onset  has  been  preceded  by  mental  anxiety,  strain,  etc. 
In  a  small  proportion  of  cases  the  patients  have  suffered  from  a 
prolonged  drain  of  blood.  A  profound  form  of  anaemia,  somewhat 
similar  to  that  characteristic  of  pernicious  anaemia,  appears  some- 
times to  be  developed  as  the  result  of  long-continued  malarial 
poisoning.  In  two  of  my  cases  the  disease  seemed  to  have  its 
starting  point  in  an  attack  of  yellow  fever.  A  profound  condition 
of  anaemia,  resembling  pernicious  anaemia,  may  also  be  developed 
after  prolonged  lactation,  pregnancy  and  parturition.  In  some  of 
these  cases  the  anaemia  is  without  doubt  of  the  pernicious  form,  but 
in  others  it  would  appear  to  be  of  the  simple  (chlorotic  or  secondary) 
type  ;  probably,  therefore,  the  importance  of  pregnancy  and  lacta- 
tion as  causes  of  pernicious  anaemia  has  been  exaggerated.  In 
some  cases,  intestinal  parasites  (the  ankylostoma  duodenale  and 
the  bothriocephalus  latus)  have  been  found  in  the  intestine.  A 
profound  form  of  anaemia,  which  in  many  of  its  clinical  features 
closely  resembles  pernicious  anaemia,  was  very  prevalent  amongst 
the  miners  in  the  St  Gothard  tunnel,  and  was  proved  to  be  due 
to  the  ankylostoma  duodenale  ;  in  these  cases  the  anaemia  seems, 
in  part  at  least,  to  be  the  direct  result  of  the  abstraction  of  blood 
from  the  intestinal  mucous  membrane.  In  some  cases,  the  con- 
dition appears  to  be  developed  in  patients  affected  with  cancer  of 
the  stomach,  but  this  is  rare  ;  in  the  great  majority  of  cases  of  this 
description  there  seems  to  be  little  doubt  that  the  anaemia  (judging 
from  the  characters  of  the  blood)  is  of  the  "  secondary  "  type. 

Mode  of  Onset. — The  onset  is  usually  slow  and  gradual,  but 
in  exceptional  cases  (and  the  jaundiced  case  to  which  I  have 
already  referred  was  a  case  in  point)  the  disease  is  rapidly  deve- 
loped and  the  patient  becomes  profoundly  anaemic  and  manifests 
all  the  symptoms  characteristic  of  an  advanced  stage  of  the  disease 
in  the  course  of  two  or  at  most  three  months. 

Morbid  Anatomy. 

Before  considering  the  exact  manner  in  which  the  anaemia  is 
produced,  it  may  perhaps  be  well  to  direct  attention  to  the  morbid 
anatomy  of  the  disease. 

The  bodies  of  patients  who  have  died  of  pernicious  anaemia  are 
remarkably  bloodless ;  the  brain  is  probably  more  anaemic  than  in 
any  other  condition,  death  from  haemorrhage  not  excepted.  In 
more  than  one  case  I  have  diagnosed  pernicious  anaemia  in  the 
post-mortem  room  from  the  bloodless  condition  of  the  brain  alone 
(without  of  course   knowing    anything  of  the   clinical   history   or 


-8  DISEASES   OF   THE   BLOOD. 

seeing  the  whole  of  the  post  mortem — going  into  the  pathological 
theatre  and  seeing  the  exposed  brain,  I  have,  from  the  remarkably 
bloodless  condition,  said  to  the  pathologist,  "  That  is  surely  a  case 
of  pernicious  anaemia").  The  heart  and  large  vessels  usually  con- 
tain extremely  little  blood. 

The  subcutaneous  fat  is  usually  well  preserved  and  in  most  cases 
of  a  lemon  or  canary  yellow  colour.  In  some  cases  the  tissues  are 
distinctly  bile-stained.  The  subcutaneous  tissues  of  the  feet  and 
legs  and  eyelids,  more  especially  the  upper  eyelids  (and  it  may  be 
of  the  body  generally,  though  this  is  not  usually  the  case),  may  be 
slightly  cedematous.  The  internal  cavities  (pericardium,  pleura, 
much  less  frequently  the  peritoneum)  may  contain  a  certain  amount 
of  dropsical  effusion,  though  this  is  not  as  a  rule  extensive. 

The  somatic  muscles  are  usually  somewhat  wasted  ;  in  some 
cases  they  are  of  a  deep  red  colour,  like  the  muscles  of  a  horse  ;  in 
others — and  this  in  my  experience  is  more  common — they  are  paler 
than  normal. 

Small  petechial  extravasations  are  in  the  great  majority  of  cases 
present  in  the  retina  and  in  many  cases  in  the  pericardium,  pleura, 
beneath  the  endocardium,  and  peritoneum,  sometimes  in  the  skin, 
less  frequently  on  the  surface,  or  in  the  substance,  of  the  brain,  etc. 
In  rare  cases  more  extensive  haemorrhages  have  been  noted  on  the 
surface  of  the  brain,  etc. 

The  heart  muscle  is  usually  in  a  condition  of  advanced  fatty 
degeneration  ;  there  is,  in  fact,  no  disease  in  which  such  splendid 
examples  of  fatty  degeneration  of  the  heart  are  found  as  pernicious 
anaemia.     The  cardiac  cavities  are  usually  more  or  less  dilated. 

In  some  cases,  the  lungs  are  pale,  dry  and  emphysematous  ;  in 
others,  cedematous. 

In  a  considerable  proportion  of  cases,  morbid  changes  are 
present  in  the  stomach  or  intestine.  The  mucous  membrane  of  the 
stomach  is  sometimes  atrophied  ;  in  others  affected  with  fibroid 
changes.  In  three  of  my  cases  it  presented  a  mammillated  appear- 
ance towards  the  pylorus,  and  the  same  condition  has  been  noted 
by  other  observers.  In  some  cases,  as  Samuel  Fenwick  and  ethers 
have  pointed  out,  the  gastric  tubules  are  affected  with  fatty  degene- 
ration or  completely  atrophied.  Ulceration  of  the  intestine  is 
sometimes  present ;  I  have  seen  it  in  several  instances.  The 
mucous  coat  of  the  small  intestine  is  also  in  many  cases  atrophied  ; 
but  this  is  often  masked  by  an  cedematous  condition  which  is  pro- 
bably developed  in  many  instances  shortly  before  death.  Worms 
or  other  parasites  are  occasionally  found  in  the  intestine.  Changes 
have  been  described  in  the  pancreas  and  in  the  abdominal  sympa- 


PERNICIOUS   ANAEMIA.  79 

thetic,  but  they  are  probably  accidental  or  secondary  to  the  anaemic 
condition. 

The  spleen  is  in  some  cases  somewhat  enlarged  ;  in  others 
shrunken.  Dr  Hunter  has  suggested  that  the  difference  depends 
upon  the  condition  as  regards  blood  destruction  which  was  going 
on  just  before  death. 

The  liver  is  usually  enlarged  and  markedly  fatty.  On  micro- 
scopical examination  it  presents,  in  most  typical  cases,  a  highly 
important  and  characteristic  alteration,  viz.,  the  presence  of  yellowish 
brown  pigment  granules  situated  within  the  liver  cells.  The  pig- 
mentation is  usually  most  marked  in,  or  confined  to,  the  outer 
two -thirds  of  the  portal  area.  This  pigment  contains  iron  in  a 
comparatively  simple  combination,  so  that  when  treated  with 
hydrochloric  acid  and  ferrocyanide  of  potassium  the  Prussian  blue 
colour  is  obtained.  Sulphide  of  ammonium  blackens  the  granules. 
In  some  cases,  the  amount  of  iron  in  the  liver  has  been  ascertained 
to  be  ten  times  the  normal.  According  to  Dr  William  Hunter, 
this  change  (excess  of  iron  and  its  peculiar  characters  and  distri- 
bution in  the  cells  of  the  liver)  is  characteristic  and  pathognomonic 
•of  pernicious  anaemia.  In  two  of  the  cases  which  I  described  many 
years  ago,  I  recognised  the  abnormal  pigmentation  and  its  peculiar 
distribution,  but  I  did  not  attach  any  importance  to  it.  In  all  of 
my  recent  cases  in  which  a  post-mortem  examination  was  obtained, 
a  considerable  excess  of  iron  was  present  in  the  liver  and  in  some 
instances  also  in  the  spleen  and  kidney. 

Whether  this  excess  of  iron  in  the  liver  is,  as  Dr  Hunter  sup- 
poses, a  constant  feature  of  pernicious  anaemia  remains  to  be  proved 
by  further  information.  In  one  case  which  presented  all  the  typical 
clinical  characters  of  pernicious  anaemia,  Dr  W.  B.  Ransom  found 
no  excess  of  iron  in  the  liver  after  death.  As  I  will  presently  point 
out,  the  question  has  not  as  yet  been  definitely  decided  whether  the 
•clinical  condition  pernicious  anaemia  is  always  due  to  excessive 
blood  destruction  in  the  portal  area  or  not ;  if  it  is  not  always  due 
to  excessive  blood  destruction  in  the  portal  area,  it  must  of  course 
be  admitted  that  an  excess  of  iron  in  the  liver  is  not  an  essential 
feature  of  the  disease. 

The  kidneys  are  usually  enlarged,  the  cortex  pale,  the  epithelium 
of  the  tubules  fatty  ;  deposits  of  pigmented  granules  containing  iron 
are  in  some  cases  present  within  the  tubules,  and,  when  well  marked, 
present  a  highly  striking  and  characteristic  appearance. 

The  marrow  of  the  bones  is  usually  (?  always)  more  or  less  dis- 
tinctly altered  ;  the  yellow  marrow  of  the  long  bones  (the  femur, 
for  example)  is  replaced  by  red  marrow  and  the  marrow  tissue  is 


So  DISEASES   OF   THE   BLOOD. 

evidently  in  a  state  of  active  change  and  proliferation.  Instead 
of  presenting  the  yellow  fatty  appearance  of  the  bone-marrow  of 
the  adult,  the  marrow  is  of  a  deep  red  or  violaceous  colour  like  the 
marrow  of  the  fcetus.  On  microscopical  examination,  the  fat  may 
have  for  the  most  part,  or  entirely,  disappeared  and  the  marrow 
may  contain  an  enormous  increase  of  nucleated  red  corpuscles  ; 
while  the  marrow  cells  may  be  much  less  numerous  than  normal. 
In  some  cases,  enormous  nucleated  red  blood  corpuscles  ("  giganto- 
blasts  "),  which  are  not  found  in  the  normal  marrow,  are  present  in 
large  numbers.  There  may  also  be  some  absorption  of  the  bone 
trabecular.  In  all  of  my  cases  in  which  the  condition  of  the  bone 
marrow  was  noted,  these  characteristic  alterations  were  present. 

Dr  Muir  sums  up  his  observations  on  the  condition  of  the  bone- 
marrow  in  a  series  of  five  cases  of  pernicious  anaemia  as  follows  : — 

"  i.  The  changes  most  frequently  observed  in  the  marrow  in  pernicious 
anaemia  may  be  said  to  be  :  (a)  increased  number  of  nucleated  red  corpuscles 
in  the  marrow  ;  (b)  transformation  of  the  fatty  marrow  in  the  shafts  of  the  long 
bones  into  red  marrow  ;  (c)  absorption  of  the  bone  trabecular  between  the  red 
marrow. 

"  2.  A  further  change,  which  may  be  found  in  the  long-standing  cases,  is 
the  occurrence,  in  large  numbers,  of  large  nucleated  red  corpuscles  (giganto- 
blasts),  reaching  io\x.  or  even  more  in  diameter,  often  with  fragmented  and 
apparently  degenerated  nuclei.  Along  with  these  is  generally  a  distinct  pre- 
ponderance of  coloured  over  colourless  elements  in  the  marrow.  The  condition 
of  the  marrow  in  this  advanced  stage  appears  to  be  peculiar  to  pernicious 
anaemia. 

"  3.  The  newly  formed  marrow  in  its  cellular  constituents  and  structural 
arrangement  closely  resembles  normal  marrow.  The  eosinophile  cells  are 
specially  few  at  first,  but  become  more  numerous  afterwards.  The  giant  cells, 
whose  development  can  be  traced  from  marrow  cells,  are  generally  compara- 
tively small  and  few  in  number. 

"4.  In  the  transformation  of  the  fatty  into  the  red  marrow  there  are  two 
main  factors,  viz.,  a  widening  of  certain  capillaries  to  form  'venous  capillaries,' 
and  an  accumulation  of  marrow  cells  (leucocytes)  around  them.  Afterwards  the 
demarcation  of  the  vessels  becomes  deficient,  and  the  usual  marrow  structure  is 
reached. 

"  5.  No  special  cells  are  concerned  in  the  process  of  the  absorption  of  bone 
which  occurs  ;  gradual  softening  and  simple  atrophy  appear  to  take  place, 
associated  with  the  hyperplasia  of  the  marrow. 

"6.  Pigment,  much  of  which  gives  the  iron  reaction,  may  be  present  in  the 
newly  formed  marrow  in  considerable  amount,  occurring  both  in  the  free  state 
and  also  within  cells.  I  have  found  it  specially  abundant  where  the  an;cmiahas 
been  severe  and  progressing  at  the  time  of  death. 

"  7.  The  earlier  changes  can  only  be  interpreted  as  an  extension  of  blood- 
forming  tissue  of  compensatory  nature,  due  to  blood  destruction  ;  the  changes 
id)  and  (b)  being  similar  to  those  produced  by  haemorrhage,  and  also  found  in 
other  diseases. 


PERNICIOUS   AN/EMIA.  8l 

"  8.  The  further  changes  found  in  advanced  cases  (2)  are  also  secondary, 
and  are  due  to  a  long  continuance  of  the  same  conditions,  the  nucleated  red 
corpuscles  showing  a  return  to  an  embryonic  type."  * 

Whether  these  changes  in  the  bone-marrow  are  constant  or  not 
in  cases  of  pernicious  anaemia  is,  however,  another  point  ;  in  some 
of  the  cases  which  have  been  examined  they  have  been  only  slightly 
marked  or  (?)  altogether  absent.  Further,  these  same  changes  have 
been  observed  in  other  conditions  than  pernicious  anaemia  (other 
forms  of  profound  anaemia,  cancer,  etc.) ;  consequently  they  cannot 
be  regarded,  so  far  as  our  present  knowledge  enables  us  to  judge,, 
as  pathognomonic  of  the  disease. 

Pathological  changes  are  sometimes  present  in  the  spinal  cord. 
In  most  cases  in  which  the  cord  lesion  is  advanced  and  marked,  a 
condition  of  postero-lateral  sclerosis,  very  similar  in  appearance 
and  distribution  (as  Dr  Risien  Russell  has  pointed  out)  to  the  lesions 
in  cases  of  ataxic-paraplegia,  is  present.  In  some  cases,  the  posterior 
columns  are  sclerosed  very  much  in  the  same  way  as  they  are  in 
locomotor  ataxia.  In  others,  again,  the  crossed  or  direct  pyramidal 
tracts  are  sclerosed.  In  some  cases,  the  cord  changes  consist  of 
scattered  patches  of  myelitis,  perhaps  produced  around  minute 
petechial  haemorrhages.  It  remains,  however,  to  be  shown  whether 
in  all  of  the  cases  such  as  Dr  Taylor  has  described  (in  which 
the  pathological  changes  in  the  spinal  cord  were  very  marked  and 
striking)  the  anaemia  was  the  cause  of  the  cord  changes  ;  and,  if 
so,  whether  the  anaemia  was  "pernicious."  Dr  Taylor  thinks  that 
these  extensive  cord  lesions  are  probably  the  result  of  some  toxic 
substance.  This  view  seems  to  me  very  probable,  though  some 
of  the  sclerotic  changes  in  the  spinal  cord  are  perhaps  developed 
around,  and  as  the  result  of,  minute  petechial  haemorrhages. 

The  brain,  as  has  been  already  stated,  is  remarkably  bloodless  ; 
and  I  have  little  doubt  that  careful  microscopical  examination  will 
show  pathological  changes  in  the  brain  tissues,  more  especially  in  the 
nerve  cells.  In  one  case,  which  came  under  my  notice  some  years 
ago,  numerous  small  petechial  haemorrhages  were  present  both  on 
the  surface  and  in  the  substance  of  the  brain. 

In  Vol.  47,  Guy's  Hospital  Reports  (1890)  Dr  Hale  White  gives 
a  valuable  abstract  of  the  post-mortem  findings  in  all  the  cases 
of  pernicious  anaemia  (31  in  number)  which  have  died  in  Guy's 
Hospital  from  1855  to  1889,  both  years  inclusive. 


*  "  The  Journal  of  Pathology  and  Bacteriology,"  February  1894. 

F 


82  DISEASES   OF   THE   BLOOD. 


Pathological  Physiology. 

There  is  still  considerable  difference  of  opinion  as  to  the  exact 
manner  in  which  the  anaemia  is  produced — in  other  words,  as  to  the 
exact  nature  and  causation  of  the  condition  which  is  termed  per- 
nicious anaemia.  In  the  present  state  of  our  knowledge  it  is  perhaps 
impossible  to  come  to  a  positive  conclusion  and  to  give  an  explana- 
tion which  will  embrace  all  cases.  In  considering  the  nature  and 
causation  of  the  disease,  the  following  questions  have  to  be  taken 
into  account : — 

i.  Is  the  condition  which  we  term  pernicious  anaemia  a  sepa- 
rate and  distinct  disease,  a  definite  clinical  entity,  or  may  the  clinical 
condition  which  we  term  pernicious  anaemia  be  the  result  of  several 
different  pathological  conditions  and  morbid  states  ? 

2.  Is  the  anaemic  condition  the  result  of  blood  destruction  or 
defective  blood  formation. 

3.  What  is  the  fundamental  and  underlying  cause  of  the  con- 
dition ? 

All  of  these  questions  are  more  or  less  intimately  bound  up 
together,  and  it  is  difficult  to  answer  one  without  considering  and 
trying  to  answer  the  others.  In  the  present  state  of  our  knowledge 
it  is  perhaps  impossible  to  give  a  decided  and  dogmatic  answer  to 
any  one  of  them. 

Dr  William  Hunter  is  of  opinion  that  there  is  a  separate  and 
distinct  disease,  pernicious  anaemia  ;  that  it  is  due  to  blood  destruc- 
tion ;  that  the  blood  destruction  takes  place  chiefly  in  the  portal 
circulation  ;  and  that  the  blood  destruction  is  the  result  of  the 
absorption  of  some  poisonous  substance,  probably  a  chemical  sub- 
stance or  cadaveric  ptomaine,  produced  in  the  intestine  by  some 
definite  and  specific  micro-organism. 

He  thinks  that  the  blood  destruction  chiefly  occurs  in  the  spleen 
and  liver ;  and  that  the  iron  which  is  liberated  from  the  red 
corpuscles  which  are  destroyed  in  the  spleen  is  carried  to  the  liver 
and  is  there  stored  up  in  the  liver  cells  in  the  outer  two-thirds  of 
the  portal  area. 

Dr  Hunter  therefore  supposes  that  the  poison  which  is  absorbed 
from  the  intestine  causes  destruction  of  the  red  blood  globules  in 
the  spleen  and  has  an  effect  on  the  liver  cells  which  leads  them  to 
store  up  the  iron  in  the  form  of  pigment  granules — in  other  words, 
to  functionate  in  an  abnormal  manner. 

Dr  Hunter  summarises  his  conclusions  in  the  following  propo- 
sitions : — 


PERNICIOUS   AN/EMIA.  83 

"  1.  Pernicious  anaemia  is  to  be  regarded  as  a  special  disease  both  clinically 
and  pathologically.     It  constitutes  a  distinct  variety  of  idiopathic  anaemia. 

"2.  Its  essential  pathological  feature  is  an  excessive  destruction  of  blood. 

"  3.  The  most  constant  anatomical  change  to  be  found  is  the  presence  of  a 
large  excess  of  iron  in  the  liver. 

"4.  This  condition  of  the  liver  serves  at  once  to  distinguish  pernicious 
anaemia  post  mortem  from  all  varieties  of  symptomatic  anaemia,  as  also  from  the 
anaemia  resulting  from  loss  of  blood. 

"  5.  The  blood  destruction  characteristic  of  this  form  of  anaemia  differs  both 
in  its  nature  and  its  seats  from  that  found  in  malaria,  in  paroxysmal  haemo- 
globinuria,  and  other  forms  of  haemoglobinuria. 

"  6.  The  view  can  no  longer  be  held  that  the  occurrence  of  hcemoglobinuria 
simply  depends  on  the  quantity  of  haemoglobin  set  free. 

"  7.  On  the  contrary,  the  seat  of  the  destruction  and  the  form  assumed  by 
the  hcenwglobin  on  being  set  free  are  important  conditions  regulating  the  pre- 
sence or  absence  of  haemoglobinuria  in  any  case  in  which  an  excessive  dis- 
integration of  corpuscles  has  occurred. 

"  8.  In  paroxysmal  haemoglobinuria  the  disintegration  of  corpuscles  occurs  in 
the  general  circulation,  and  is  due  to  a  rapid  dissolution  of  the  red  corpuscles. 

"9.  In  pernicious  anaemia  the  seat  of  disintegration  is  chiefly  the  portal 
circulation,  more  especially  that  portion  of  it  contained  within  the  spleen  and 
the  liver,  and  the  destruction  is  effected  by  the  action  of  certain  poisonous 
agents,  probably  of  a  cadaveric  nature,  absorbed  from  the  intestinal  tract."  * 

Dr  Hunter  regards  the  changes  in  the  bone-marrow  as  secondary 
to  the  blood  destruction  ;  and  with  this  opinion  I  entirely  agree,  at 
all  events  so  far  as  the  great  majority  of  cases  are  concerned  ;  at 
the  same  time  it  is  I  think  quite  possible  that  future  observations 
may  show  that  a  condition  of  blood  identical  with  that  of  pernicious 
anaemia  (in  other  words  the  clinical  condition  which  we  term  per- 
nicious ansemia)  may  perhaps  in  rare  instances  be  due  to  a  primary 
lesion  of  the  bone-marrow. 

Before  I  became  acquainted  with  Hunter's  observations,  I  was 
in  the  habit  (with,  I  suppose,  most  other  clinicians  and  patho- 
logists) of  regarding  the  great  diminution  in  the  number  of  the  red 
blood  corpuscles,  which  is  the  essential  characteristic  of  pernicious 
anaemia,  as  the  result  of  defective  blood  formation.  The  presence 
of  large  numbers  of  immature  red  blood  corpuscles  and  the  occa- 
sional occurrence  in  the  blood  of  nucleated  red  blood  corpuscles 
seemed  to  me  to  be  strongly  in  favour  of  this  view — defective 
formation  rather  than  of  increased  destruction.  At  the  time  when 
Dr  Hunter  first  told  me  of  his  experiments  and  observations,  I  had 
the  advantage  of  his  assistance  in  the  Out-Patient  Department  of 
the  Edinburgh  Royal  Infirmary.     I  put  the  following  questions  to 

*  An  Investigation  into  the  Pathology  of  Pernicious  Anaemia,  Lancet, 
Sept.  22,  29  and  Oct.  6,  1888. 


84  DISEASES   OF   THE    BLOOD. 

him,  "  How  do  you  account  for  the  large  number  of  immature  red 
blood  corpuscles  in  the  blood  ?  "  and  "  Are  not  these  immature  red 
corpuscles  indicative  of  defective  blood  formation  rather  than  exces- 
sive blood  destruction  ?  "  He  met  this  by  saying  that  if  you  have 
excessive  destruction  of  red  blood  corpuscles  at  one  end  of  the 
circulation  {i.e.,  in  the  portal  circulation),  this  will  necessarily  give 
rise  to  excessive  production  at  the  other  (i.e.,  in  the  bone-marrow)  ; 
in  other  words,  he  allowed  that  there  was  defective  blood  formation, 
but  he  explained  the  defective  formation  of  the  red  blood  globules 
as  the  result  of  the  excessive  strain  thrown  on  the  blood-forming 
tissues — the  bone-marrow — in  consequence  of  the  excessive  blood 
destruction  which  he  argued  was  the  essential  cause  of  the  anaemia. 
This  argument,  which  supposes  that  a  large  number  of  immature 
and  imperfect  red  blood  cells  are  thrown  into  the  circulation  in 
order  to  meet,  as  it  were,  and  compensate  the  excessive  blood 
destruction  which  is  going  on  at  the  other  end  of  the  circulation, 
seems  to  me  a  satisfactory  explanation  ;  but  the  question  is  whether 
it  represents  the  whole  truth. 

It  is  quite  possible,  I  think,  that  in  many  cases  of  pernicious 
anaemia  the  diminution  of  the  red  blood  corpuscles  is  the  result 
both  of  excessive  blood  destruction  and  defective  blood  formation. 
Even  if  we  admit  with  Dr  Hunter  that  in  the  great  majority  of 
cases  of  pernicious  anaemia  the  primary  cause  of  the  anaemia  is 
excessive  blood  destruction,  it  must  also  I  think  be  allowed  that,  in 
the  later  stages  of  the  disease  at  all  events,  there  is  imperfect  and 
defective,  or  perhaps  it  is  more  correct  to  say  too  rapid  and  there- 
fore imperfect,  blood  formation  in  the  bone-marrow.  Now,  it  is 
not  difficult  to  conceive,  if  this  condition  (too  rapid  and  therefore 
imperfect  formation  of  red  blood  corpuscles,  due  to  an  excessive 
and  pathological  strain,  so  to  speak,  on  the  blood-forming  tissue — 
the  bone-marrow)  continues  and  lasts,  as  we  know  it  must  do,  for 
long  periods  of  time,  that  an  actual  diseased  condition  of  the  bone- 
marrow  may  ultimately  become  produced.  We  may  suppose  that 
there  is,  in  the  first  instance,  as  the  result  of  the  excessive  strain 
which  is  thrown  upon  the  bone-marrow,  a  condition  of  irritable 
weakness  ;  and  that  this,  which  is  at  first  a  functional  condition,  as 
in  many  other  cases  of  irritable  weakness,  may  ultimately  pass  on 
to  organic  disease.  It  seems  to  me  probable  that  although  the 
fundamental  change  in  typical  cases  of  pernicious  anaemia  (those — 
and  they  seem  to  comprise  the  vast  majority  of  cases — in  which 
there  is  an  excess  of  iron  in  the  liver)  is  the  result  of  exces- 
sive blood  destruction  in  the  portal  circulation,  the  defective 
blood  formation  in  the  bone-marrow  is  an  important  consideration 


PERNICIOUS   AN/EMIA.  85 

which  cannot  be  ignored.  To  cases  of  this  kind  in  which  there  is 
an  excess  of  iron  in  the  liver,  the  term  " gastro-intestinal-hepatic 
type  of  hemolytic  ancemia  "  may  I  think  be  appropriately  applied. 
I  think  it  probable  that  even  in  these  cases — the  Hunterian  type 
of  the  disease,  as  I  am  in  the  habit  of  terming  it — a  double  cause 
for  the  bloodlessness  is  present,  viz.,  increased  blood  destruction  in 
the  portal  circulation  and  too  rapid  and  therefore  defective  blood 
formation  in  the  bone-marrow. 

Further,  as  I  have  already  suggested,  it  is  perhaps  the  case — 
though  this  requires  to  be  definitely  proved — that  in  some  cases  a 
primary  lesion  of  the  marrow  of  the  bone  may  lead  to  the  produc- 
tion of  a  form  of  anaemia  which  is  very  closely  allied  to,  if  not 
identical  with,  the  pernicious  variety  of  the  disease.  If  this  is  so, 
we  may  term  these  cases  the  myeloid  type  of  pernicious  antzmia  of 
homogenetic  origin.  And  in  this  connection  it  is  interesting  to  note 
that  so  long  ago  as  the  year  1875  Professor  Pepper  of  Philadelphia, 
who  was  one  of  the  first  to  direct  attention  to  the  changes  in  the 
bone-marrow,  proposed  the  term  "  myelogenous  anaemia "  or  the 
"  medullary  form  of  pseudo-leukaemia  "  for  the  disease. 

If  it  should  be  proved,  as  I  have  suggested  above,  that  ex- 
cessive blood  destruction,  however  produced,  may  ultimately,  pro- 
vided only  that  it  is  continuous  and  suificiently  long  continued,  lead 
to  an  abnormal  and  diseased  condition  of  the  red-blood-forming 
tissue  (the  bone-marrow),  it  must  be  allowed  that  the  group  of 
clinical  symptoms  to  which  we  give  the  term  pernicious  anaemia 
may  be  due  to  a  variety  of  processes,  i.e.,  may  be  the  ultimate  result 
of  many  conditions. 

I  am  not  then  prepared  to  deny  (for  I  think  before  this  is 
granted  further  information  is  required)  that  a  drain  of  blood,  which 
lasts  continuously  for  a  sufficiently  long  period  of  time,  may  not 
ultimately  perhaps  produce  a  form  of  anaemia  which  is  clinically 
identical,  so  far  as  the  condition  of  the  blood  is  concerned  and  so 
far  as  our  present  methods  of  clinical  examination  enable  us  to 
judge,  with  pernicious  anaemia. 

That  the  most  marked  poikilocytosis  may  occur  as  the  result 
of  a  long-continued  drain  of  blood  is  shown  by  the  following  case 
which  came  under  my  observation  some  years  ago.  The  patient 
had  suffered  for  years  from  a  bloody  vaginal  discharge,  the  result 
of  a  diseased  condition  of  the  ovary  and  uterus.  She  was  pro- 
foundly anaemic,  the  red  blood  corpuscles  were  greatly  reduced  in 
number  and  of  all  shapes  and  sizes,  in  many  of  them  the  haemo- 
globin was  concentrated  in  a  localised  area  of  the  corpuscle ;  in 
short  the  microscopic  condition  of  the  red  blood  globules  exactly 


86  DISEASES   OF   THE   BLOOD. 

corresponded  to  that  which  is  characteristic  of  pernicious  anaemia. 
(I  have  no  note  of  the  condition  of  the  white  corpuscles,  of  the 
percentage  of  haemoglobin,  or  of  the  "colour  index.")  In  this  case 
the  excessive  and  long-continued  loss  of  red  blood  corpuscles  from 
the  uterus  was  apparently  the  cause  of  an  excessive  and  imperfect 
formation  of  red  blood  corpuscles  in  the  bone-marrow,  while  the 
resulting  anaemia  was  an  anaemia  which,  clinically  speaking,  seemed 
to  me  at  the  time  to  correspond  to  the  usual  type  of  the  disease. 
Whether  the  blood  characters,  if  they  had  been  examined  by 
modern  and  improved  methods  of  research,  would  have  been  iden- 
tical with  those  of  pernicious  anaemia,  I  am  not  of  course  prepared 
to  say. 

But  notwithstanding  this  suggestion  (that  a  drain  of  blood  if 
sufficiently  severe  and  long  continued  may  perhaps  produce  a 
clinical  condition  corresponding  to  that  characteristic  of  pernicious 
anaemia),  I  am  quite  unable  to  agree  with  the  theory  which  Pro- 
fessor Stockman  has  advanced  that  pernicious  anaemia  is  due  to 
the  small  capillary  haemorrhages  which  are  so  often  found  after 
death  in  fatal  cases  of  the  disease.  I  look  upon  these  capillary 
haemorrhages  as  a  consequence — the  result  and  not  the  cause  of  the 
anaemia.  In  proof  of  this  it  is,  I  think,  only  necessary  to  state : — 
That  in  many  cases  of  pernicious  anaemia  very  few  petechial 
haemorrhages  are  found  after  death  ;  that  there  is  no  corre- 
spondence between  the  number  of  petechial  haemorrhages  found 
after  death  and  the  degree  of  the  anaemia ;  in  some  of  my  most 
marked  cases  of  pernicious  anaemia  there  were  practically  no 
petechial  haemorrhages  present ;  that  the  petechial  haemorrhages 
which  we  can  see  during  life  (the  retinal  haemorrhages  and  the 
petechial  haemorrhages  which  are  occasionally  though  rarely  seen 
in  the  skin  and  subcutaneous  tissues  in  the  advanced  stages  of  the 
disease)  are  not  developed  in  the  early  stages  of  the  disease,  but 
only  when  the  anaemia  becomes  marked  ;  and  that  in  other  diseases 
in  which  numerous  petechial  and  other  haemorrhages  are  developed, 
and  recurringly  developed  for  long  periods  of  time,  as  in  some  cases 
of  Henoch's  purpura  for  example — and  I  will  afterwards  record  a 
case  in  point — the  symptoms  and  blood  conditions  characteristic  of 
pernicious  anaemia  are  not  developed. 

Now,  if  a  form  of  anaemia  undistinguishable  during  life,  except 
by  its  mode  of  causation,  from  progressive  pernicious  anaemia,  can 
ultimately  result  from  a  long-continued  loss  of  blood,  there  is  no 
reason  to  suppose  that  in  such  a  case  the  liver  would  contain  art 
excess  of  iron  pigment. 

Hunter,  if  I   understand  him  aright,  would  exclude  from   the 


PERNICIOUS   AN/EMIA.  87 

category  of  pernicious  anaemia  all  cases  of  anaemia  in  which  there 
is  no  excess  of  iron  in  the  liver.  But  it  seems  to  me  that  further 
information  is  required  before  this  proposition  can  be  absolutely 
accepted,  though  I  admit  that  it  applies  to  the  vast  majority  of 
cases.  At  the  Newcastle  Meeting  of  the  British  Medical  Associa- 
tion, Dr  W.  B.  Ransom  brought  before  the  Medical  Section  a  case 
in  which  all  the  characteristic  symptoms  of  pernicious  anaemia  were 
present  during  life  and  in  which  no  excess  of  iron  in  the  liver  was 
found  after  death. 

And  even  if  Hunter's  view  (that  pernicious  anaemia  is  a  separate 
and  distinct  clinical  entity)  is  correct,  the  clinical  physician  would 
still  be  left  in  doubt  and  perplexity  as  regards  the  diagnosis  of  some 
cases  during  life  ;  for,  if  I  understand  him  correctly,  Hunter  regards 
the  condition  of  the  liver,  in  respect  to  the  presence  or  absence  of 
an  excess  of  iron,  as  the  fundamental  characteristic  of  the  disease. 
He  considers  that  those  cases  of  anaemia  in  which  the  liver  contains 
a  great  excess  of  iron  during  life  are  cases  of  pernicious  anaemia ; 
but  that  those  cases  in  which  there  is  no  excess  of  iron  in  the  liver 
are  not.  But  even  if  this  point  be  granted,  the  condition  of 
the  liver  is  a  post-mortem  change  which  cannot  be  determined 
during  life,  unless  the  new  photography  can  demonstrate  its  pre- 
sence ;  but  this,  as  Dr  Gulland  has  pointed  out  to  me,  is  very 
unlikely  since  the  iron  in  the  liver  is  in  organic  combination.  In 
short,  as  I  have  already  stated,  in  the  present  position  of  our  know- 
ledge, it  is  perhaps  premature  to  conclude  that  a  profound  anaemia 
which  proves  fatal  and  in  which  there  is  no  excess  of  iron  in  the 
liver  is  never  pernicious. 

I  doubt,  too,  whether  we  can  absolutely  rely  upon  the  condition 
of  the  urine  as  a  clinical  test  of  pernicious  anaemia.  So  far  as  my 
experience  enables  me  to  judge,  a  highly  pigmented  condition  of 
the  urine  is  often  absent  ;  and  even  in  those  cases  in  which  it  is 
present,  it  is  usually  merely  temporary  and  evanescent. 

Further,  if  future  observation  should  show  that  a  condition 
undistinguishable  during  life  from  pernicious  anaemia  may  be  the 
result  of  long-continued  haemorrhage,  it  may  further,  perhaps,  be 
allowed  that  the  same  group  of  clinical  symptoms  (which  we  regard 
as  characteristic  of  pernicious  anaemia)  may  sometimes  be  due  to 
long-continued  diarrhoea  and  perhaps  to  other  conditions  which  lead 
to  long-continued  and  excessive  blood  destruction  on  the  one  hand, 
and  which  consequently  throw  a  long-continued  and  abnormal  strain 
upon  the  blood-forming  tissue  (the  marrow  of  the  bones)  on  the 
other.  Again,  it  seems  certain  that  a  condition  closely  resembling, 
though  it  may  perhaps  be  doubted  whether  it  is  identical    with 


88  DISEASES   OF   THE   BLOOD. 

pernicious  anaemia  may  bs  the  result  of  intestinal  parasites.  Further, 
it  has  been  stated  that  in  some  cases  which  commence  as  chlorosis, 
a  condition  of  pernicious  anaemia  is  ultimately  established.  The 
exact  nature  of  these  transitional  cases  is  doubtful.  The  blood 
seems  seldom  to  have  been  examined  with  sufficient  accuracy  to 
make  sure  of  either  the  original  or  ultimate  diagnosis  ;  but  Case  31 
of  my  series  seems  a  case  in  point. 

The  same  statement  perhaps  also  applies  to  some  cases  of 
gastric  cancer. 

I  am,  then,  disposed  to  think  in  the  present  state  of  our  know- 
ledge : — 

(1.)  That  pernicious  anaemia  should  be  regarded  as  a  clinical 
condition  ;  in  other  words,  that  the  term  pernicious  anaemia  should 
be  applied  to  any  profound  and  (apparently)  causeless  anaemia 
which  is  characterised  by  the  peculiar  alterations  in  the  blood  which 
I  have  described  above,  and  in  which  the  anaemia  tends  to  pursue  a 
progressive  or  pernicious  course. 

(2.)  That  until  further  information  is  obtained,  the  question 
whether  the  clinical  condition  termed  pernicious  anaemia  may  result 
from  a  variety  of  causes,  or  whether  it  is  a  single  clinical  entity  the 
causation  of  which  is  always  one  and  the  same,  should  be  left  an 
open  one. 

(3.)  That  in  many  of  the  most  typical  cases  of  pernicious  anaemia 
the  two  conditions  (excessive  blood  destruction  and  defective  blood 
formation,  or  perhaps  it  would  be  better  to  say  too  rapid  and,  there- 
fore, defective  blood  formation)  are  probably  combined. 

(4.)  That  in  those  cases  in  which  the  condition  is  due  to  exces- 
sive blood  destruction,  the  blood  destruction  may  perhaps  be  due 
to  a  variety  of  different  causes  and  conditions  ;  though  there  seems 
good  reason  to  suppose  that  in  the  vast  majority  of  typical  cases 
the  condition  is  due,  as  Dr  Hunter  has  shown,  to  increased  blood 
destruction  in  the  portal  circulation,  and  that  this  increased  destruc- 
tion is  probably  the  result  of  the  absorption  of  some  poisonous 
substance  from  the  gastro-intestinal  tract. 

(5.)  Whether  a  true  pernicious  anaemia  can  result  from  a  long- 
continued  drain  of  blood  from  the  intestine  (as  in  cases  of  anky- 
lostoma  duodenale),  from  the  uterus,  etc.,  from  long- continued 
diarrhrea,  or  as  the  result  of  the  malarial,  syphilitic,  and  cancerous 
cachexia  must  in  the  meantime  I  think  remain  an  open  question. 

(6.)  That  the  condition  is  in  some  cases  perhaps  due  to  primary 
changes  in  the  bone-marrow  (though  this  has  not  as  yet  been 
definitely  established) ;  and,  if  so,  is  the  result  of  defective  blood 
formation. 


PERNICIOUS   ANAEMIA.  89 

Before  we  can  come  to  a  definite  conclusion  regarding  the  exact 
nature  and  causation  of  pernicious  anaemia,  it  is  essential  to  deter- 
mine (1)  whether  the  excess  of  iron  in  the  liver  which  Hunter  and 
others  have  described  is  invariably  present  in  all  fatal  cases  in  which 
the  clinical  group  of  symptoms  characteristic  of  pernicious  anaemia 
was  present  during  life ;  and  (2)  whether  such  an  excess  of  iron  in 
the  liver  is  necessarily  indicative  of  excessive  blood  destruction  in 
the  portal  circulation  alone.  It  is  only  after  these  questions  have 
been  decided  by  a  sufficiently  wide  series  of  observations  that  it 
will  be  possible  to  determine  whether  the  condition  which  we  term 
pernicious  anaemia  is  a  definite  disease,  a  single  clinical  entity, 
which  is  always  the  result  of  blood  destruction  in  the  portal  circu- 
lation, or  whether  it  may  not  be  the  ultimate  clinical  result  of  a 
number  of  different  pathological  conditions. 

The  solution  of  the  question  whether  pernicious  anaemia  is  a 
distinct  clinical  entity  or  not  and  more  especially  the  determination 
of  the  further  questions  —  if  pernicious  anaemia  is  always  due  to 
excessive  blood  destruction  in  the  portal  area,  what  is  the  exact 
nature  of  the  ptomaine  or  toxin  which  produces  that  destruction, 
and  how  is  that  toxin  or  ptomaine  produced — are  of  great  import- 
ance for  the  purposes  of  diagnosis,  prognosis  and  treatment. 

In  concluding  this  discussion  on  the  pathology  of  pernicious 
anaemia,  I  may  add  that  during  the  past  six  months  I  have  had 
the  opportunity  of  observing,  both  during  life  and  after  death,  a 
considerable  number  of  typical  cases  of  the  disease,  and  that  in  all 
of  them  an  excess,  and  with  one  exception  a  very  large  excess,  of 
iron  has  been  present  in  the  liver.  A  careful  consideration  of  these 
and  of  the  other  cases  which  have  come  under  my  notice  dur- 
ing the  past  two  years  has  led  me  to  believe  that  Dr  Hunter's 
conclusions  as  to  the  nature  and  causation  of  the  disease  are 
correct,  in  the  vast  majority  of  cases  at  all  events.  Whether  all 
cases  of  pernicious  anaemia  are  due  to  one  and  the  same  cause 
remains,  I  think,  to  be  proved  by  future  observation. 


Diagnosis. 

In  well-marked  cases  of  pernicious  anaemia,  the  diagnosis  does 
not,  as  a  rule,  present  any  difficulty.  The  clinical  features  which 
are  most  important  for  the  purposes  of  diagnosis  are  : — 

1.  The  (usually)  insidious  development  and  progressive  course, 
unless  of  course  the  disease  is  arrested  and  (?  temporarily)  cured  by 
treatment. 


go  DISEASES   OF   THE   BLOOD. 

2.  The  profound  asthenia  and  anaemia,  the  lemon  tint  of  the  skin 
with,  in  some  cases,  the  presence  of  distinct  jaundice. 

3.  The  absence  of  any  organic  disease  or  obvious  cause  of  the 
anaemia  (such  as  loss  of  blood)  to  account  for  the  anaemic  condi- 
tion— in  other  words,  the  primary  or  idiopathic  character  of  the 
anaemia. 

The  absence  of  local  or  visceral  disease  capable  of  accounting 
for  the  anaemia  is  a  most  important  diagnostic  point. 

4.  The  characters  of  the  blood,  more  especially : — (a)  the  great 
diminution  in  the  number  of  the  red  blood  corpuscles  ;  (J?)  the 
comparatively  small  diminution  of  the  haemoglobin  and  the  con- 
sequent fact  that  the  individual  red  blood  corpuscles  contain  at 
least  the  normal  amount,  and  usually  more  than  the  normal  amount, 
of  haemoglobin  ;  (c)  the  marked  alterations  in  size  and  shape  which 
the  red  blood  corpuscles  present ;  (d)  the  presence  of  apparently 
nucleated  and  in  most  cases  of  truly  nucleated  red  corpuscles  ;  (e) 
the  occasional  occurrence  of  the  small  dark  red  microcytes  described 
by  Eichhorst ;  and  (/)  the  occurrence  of  lymphocytosis  in  many 
cases,  and  probably  in  all  severe  cases. 

5.  The  retinal  haemorrhages. 

6.  The  inutility  of  iron  and  the  beneficial  effect  of  arsenic.  I 
attach  somewhat  less  importance  to  this  point  than  I  did  some 
years  ago,  for  in  more  than  one  case  of  pernicious  anaemia  which  I 
have  seen  of  recent  years  remarkable  benefit  has  speedily  resulted 
from  the  combined  use  of  iron  in  the  form  of  Robertson's  capsules, 
and  large  doses  of  liquor  arsenicalis.  I  think  it  probable  that  in 
these  cases  the  improvement  was  due  to  the  arsenic,  but  I  cannot 
of  course  say  that  the  iron  may  not  also  have  been  beneficial  ; 
in  the  cases  to  which  I  refer  it  certainly  was  not  prejudicial. 
Further,  a  few  cases  have  been  recorded  —  and  Case  7  in  my 
series  seems  a  case  in  point  —  in  which  marked  improvement 
occurred  under  the  administration  of  iron  alone.  But  speaking 
generally,  the  therapeutic  effect  of  iron  on  the  one  hand  and  of 
arsenic  on  the  other  is  undoubtedly  helpful  for  the  purposes  of 
diagnosis.  It  is  certain,  I  think,  that  in  most  cases  of  pernicious 
anaemia  iron  is  useless  and  in  many  cases  distinctly  harmful  ; 
whereas  in  many  cases  of  the  disease  (provided  they  are  seen  suffi- 
ciently early  and  the  patient  is  able  to  take  sufficiently  large  doses 
of  the  remedy;  arsenic  is  beneficial. 

7.  The  occurrence  of  febrile  attacks,  apparently  due  to  the 
anaemic  condition,  i.e.,  to  the  presence  of  a  toxin  in  the  blood  which 
is  perhaps  also  the  cause  of  the  blood  destruction  or  of  some  pro- 
duct of  blood  destruction,  and  not  due  to  any  other  (obvious)  cause. 


PERNICIOUS   AN/EMIA.  9 1 

8.  The  presence  of  dark-coloured  urine.  As  I  have  already 
stated,  excessive  pigmentation  of  the  urine  is  often  absent ;  and 
when  present  is  usually  only  temporary  and  evanescent.  Never- 
theless, I  agree  with  Dr  Hunter  in  thinking  that  the  occurrence  of 
highly  pigmented  urine,  which  in  many  cases  is  associated  with 
fever  and  a  paroxysmal  exacerbation  of  the  anaemia  and  other 
symptoms  characteristic  of  the  disease,  is,  when  present,  of  con- 
siderable diagnostic  significance.  With  reference  to  this  point  Dr 
Hunter  says  : — 

"  In  addition  to  this,  their  pathological  significance,  these  changes  are,  I  am 
inclined  to  think,  of  no  little  importance  from  a  diagnostic  point  of  view.  The 
high  colour  of  the  urine  observed,  unaccompanied  as  it  was  by  any  diminution 
in  quantity  or  any  rise  in  specific  gravity,  and  the  presence  of  granules  of 
blood-pigment  in  the  urine,  pointed  so  unmistakably  to  the  nature  of  the  patho- 
logical process  at  work  in  the  blood,  that  they  establish  conclusively  the 
diagnosis  of  the  case  as  one  of  pernicious  anaemia. 

"  One  must,  however,  in  this  connexion  guard  one's-self  against  a  miscon- 
ception that  may  not  improbably  arise.  The  urine  in  pernicious  anaemia  need 
not  always  show  these  well-marked  and,  when  present,  characteristic  changes. 
It  may  be  said,  however,  with  some  degree  of  assurance,  that  they  will  be  found 
more  or  less  marked  in  all  cases  at  some  period  or  other  of  their  history. 

"  In  all  cases,  as  in  the  foregoing  one,  there  will  be  times  corresponding 
to  the  periods  when  the  patient  is  gaining  ground,  when  the  colour  of  the 
urine  will  be  that  of  health,  and  nothing  abnormal  will  be  microscopically 
recognisable. 

"The  aggravations  of  weakness  will  always,  however,  be  evidenced  by  a 
higher  colour  of  the  urine,  it  may  be  also  by  the  appearance  of  blood-pigment 
granules  in  the  urine  ;  both  changes  marking  the  nature  of  the  process  within 
the  blood  which  is  the  occasion  of  these  attacks,  namely  excessive  haemolysis."* 

9.  The  age  and  sex  of  the  patient.  These  points  are  in  some 
cases  of  considerable  diagnostic  value,  more  particularly  in  deter- 
mining whether  a  profound  anaemia  is  the  result  of  chlorosis  or 
pernicious  anaemia. 

The  differential  diagnosis  of  chlorosis  and  pernicious 
anaemia. — I  have  already  considered  this  point  in  connection  with 
chlorosis  (see  page  47).  The  distinction  must,  as  I  have  previously 
stated,  be  chiefly  based  upon  : — (a)  The  condition  of  the  blood  ;  (b) 
the  presence  of  retinal  haemorrhages  ;  (c)  the  therapeutic  effect  of 
iron  on  the  one  hand  and  of  arsenic  on  the  other  ;  and  (d)  the  age 
and  sex  of  the  patient. 

The  difficulty  of  distinguishing  pernicious  anaemia  and  chlorosis 
is  chiefly  likely  to  arise: — (1)  in  those  cases — but  they  are  com- 
paratively rare — in  which  pernicious  anaemia  is  developed  in  a  young 

*  Observations  on  the  urine  in  pernicious  anaemia,  Practitioner,  November, 
and  December  1889. 


92  DISEASES   OF   THE   BLOOD. 

woman  {i.e.,  at  the  chlorotic  period)  ;  and  (2)  in  those  cases  of 
chlorosis — but  they  are  most  exceptional — in  which  the  chlorotic 
condition  is  developed  in  middle-aged  or  old  women  {i.e.,  after  the 
chlorotic  period),  or  in  men,  or  in  children  {i.e.,  before  the  chlorotic 
period).  In  my  314  cases  of  typical  chlorosis,  no  case  occurred 
after  the  age  of  33  (though  I  have  seen  three  or  four  cases  appa- 
rently of  idiopathic  anaemia  of  the  chlorotic  type  in  middle-aged  or 
old  women),  and  only  1 1  cases  after  the  age  of  28  ;  while  in  my 
series  of  45  cases  of  pernicious  anaemia  only  3  cases  occurred  below 
the  age  of  28.  The  facts  that  pernicious  anaemia  comparatively 
rarely  occurs  in  young  women,  whereas  chlorosis  is  essentially  a 
disease  of  young  women,  are,  therefore,  in  some  cases  of  distinct 
diagnostic  value. 

There  is  reason,  I  think,  to  believe  that  in  some  of  the  cases 
which  have  been  reported  as  cases  of  pernicious  anaemia  in  which 
recovery  took  place  under  iron,  the  condition  was  chlorosis  and 
not  pernicious  anaemia.  A  profound  and  causeless  anaemia  in  a 
young  woman  is  in  the  vast  majority  of  cases  chlorotic.  In  such 
cases  a  definite  diagnosis  of  pernicious  anaemia  should  be  given 
with  hesitation  and  should  only  be  ventured  upon  when  {a)  the 
characters  of  the  blood  are  very  definite  and  very  distinctive  of 
pernicious  anaemia  (rather  than  of  chlorosis) ;  and  {b)  when  iron 
given  in  large  doses  fails  to  produce  benefit.  Vice  versa,  in  cases 
of  profound  anaemia  in  which  rapid  improvement  results  from  the 
administration  of  iron  the  diagnosis  of  pernicious  anaemia  should 
always  be  regarded  with  suspicion,  and  this  is  more  especially  the 
case  when  the  patient  is  a  young  woman. 

The  differential  diagnosis  of  pernicious  anaemia  and  pri- 
mary heart  disease. — This  can  rarely  give  rise  to  any  difficulty. 
The  same  points  which  are  important  in  distinguishing  chlorosis 
and  primary  heart  disease  are  of  importance  here,  together  with  the 
condition  of  the  blood  and  the  fact  that  the  cardiac  symptoms  were 
developed  after  the  anaemia. 

The  differential  diagnosis  of  pernicious  anaemia  and  cancer 
of  the  stomach. — In  some  cases  of  cancer  of  the  stomach  in  which 
there  is  no  discoverable  tumour,  and  especially  in  those  cases  in 
which  the  body  of  the  stomach  is  involved,  the  orifices  being  free, 
the  symptoms  may  closely  resemble  those  of  pernicious  anaemia. 

In  both  conditions  there  is  progressive  asthenia,  anaemia  and 
more  or  less  emaciation,  without,  perhaps,  any  definite  and  dis- 
coverable organic  cause. 

In  the  great  majority  of  cases  the  differential  diagnosis  can  be 
satisfactorily  arrived  at  by  a  judicial  survey  of  the  whole  symptoms 


PERNICIOUS   AN/EMIA.  93 

and  physical  signs  of  the  case.  The  condition  of  the  blood,  the 
severity  of  the  stomach  symptoms,  the  presence  or  absence  of 
tenderness  on  pressure  over  the  region  of  the  stomach,  the  absence 
of  free  hydrochloric  acid  in  the  stomach  contents,  and  especially  of 
haematemesis,  of  a  tumour  or  localised  hardness  in  the  epigastric 
region  or  of  difficulty  in  swallowing  due  to  obstruction  of  the  lower 
end  of  the  oesophagus,  are  the  most  important  points  to  which 
attention  should  be  directed  in  doubtful  cases.  The  exact  char- 
acters of  the  blood  and  the  presence  or  absence  of  a  tumour  in  the 
region  of  the  stomach  are  the  most  important  points. 

Cabot  lays  stress  upon  the  fact  that  in  pernicious  anaemia  there 
is  no  leucocytosis,  whereas  in  cases  of  profound  anaemia  due  to 
malignant  disease  there  is  leucocytosis.  His  statement  is  as 
follows  : — "  As  will  be  seen  in  the  chapter  on  malignant  disease, 
leucocytosis  is  by  no  means  invariable  in  the  anaemia  of  cancerous 
growth,  but  in  those  cases  which  cause  such  an  anaemia  as  to  resemble 
the  counts  of  pernicious  anaemia,  leucocytosis  is  invariable."* 

The  occurrence  of  haematemesis  is  strongly  in  favour  of  cancer, 
for  in  my  experience  bleeding  from  the  stomach  is  rare  (though  it 
does  occasionally  occur)  in  cases  of  pernicious  anaemia. 

But  I  know  from  my  own  experience  that  the  differential 
diagnosis  of  pernicious  anaemia  and  of  cancer  of  the  stomach  or 
liver  is  in  some  cases  extremely  difficult,  more  especially  when  the 
patient  is  seen  in  consultation  practice  and  when  the  means  of 
ascertaining  the  exact  characters  of  the  blood  are  not  forthcoming. 

The  differential  diagnosis  of  pernicious  anaemia  and  of 
Bright's  disease. — There  is  rarely  if  ever  any  difficulty  in  dis- 
tinguishing these  conditions.  The  diagnosis  of  course  turns  upon 
the  condition  of  the  urine  (presence  of  albumen,  casts,  etc.)  on  the 
one  hand,  and  the  condition  of  the  blood  (the  presence  of  the 
alterations  characteristic  of  pernicious  anaemia)  on  the  other.  The 
latter  (the  condition  of  the  blood)  is  the  more  important,  for  in  some 
cases  of  pernicious  anaemia  the  urine  contains  albumen.  In  9  of  my 
series  of  45  cases,  albumen  was  present ;  the  amount  was  usually 
small — in  most  cases  a  trace — but  in  2  cases  it  was  considerable. 

The  differential  diagnosis  of  pernicious  anaemia  and  of 
leucocythaemia  and  pseudo-leukaemia. — This  presents  no  diffi- 
culty, except  in  children.  The  two  conditions  are  at  once  distin- 
guished  by   (a)  the   microscopical   characters    of  the   blood  ;    and 

*  "Clinical  Examination  of  the  Blood,"  p.  130. 


94  DISEASES   OF   THE   BLOOD. 

(b)  the  marked  enlargement  of  the  spleen,  or  of  the  lymphatic 
glands,  or  of  both  (spleen  and  lymphatic  glands). 

The  differential  diagnosis  of  pernicious  ansemia  and  of 
splenic  anaemia  without  leucocythaemia. — In  some  cases  in  which 
the  spleen  is  enlarged,  there  is  profound  anaemia  but  no  increase  of 
the  white  blood  corpuscles.  This  form  of  anaemia  is  extremely  rare ; 
no  case  has  come  under  my  own  observation.  The  essential  points 
of  distinction  from  pernicious  anaemia  are  the  enlargement  of  the 
spleen,  which  can,  of  course,  be  distinguished  during  life,  and  the 
characters  of  the  blood  ;  in  cases  of  splenic  anaemia  without  leuco- 
cythaemia (a)  the  haemoglobin  appears  to  be  diminished  more  than 
the  corpuscles,  in  other  words  the  anaemia  is  of  the  chlorotic  rather 
than  of  the  pernicious  type ;  and  (b)  the  red  corpuscles  do  not 
(usually)  present  the  extreme  variations  in  size  and  shape  and  the 
other  features  which  are  characteristic  of  pernicious  anaemia. 

The  differential  diagnosis  of  pernicious  anaemia  and  of 
medullary  anaemia. — In  considering  the  etiology  and  pathology  of 
pernicious  anaemia,  I  have  stated  that  in  (?  all)  cases  of  pernicious 
anaemia  of  long  standing,  pathological  changes  are  ultimately  pro- 
duced in  the  medulla  of  the  bones  ;  and  that  it  has  been  supposed 
(though  this  has  not  as  yet  been  definitely  proved)  that  a  form  of 
anaemia,  presenting  all  the  clinical  characteristics  of  pernicious 
anaemia,  may  in  rare  instances  result  from  a  primary  lesion  of  the 
bone-marrow.  I  know  of  no  means  by  which  such  a  condition 
could  be  distinguished  from  the  usual  (Hunterian)  type  of  pernicious 
anaemia  during  life,  except  by  the  presence  of  swelling  and  tender- 
ness over  the  bones  and  sternum,  and  it  is  doubtful  whether  such 
swelling  and  tenderness  are  always  and  necessarily  present. 
Whether  in  such  cases,  if  they  occur,  the  liver  contains  an  excess 
of  iron  or  not  is,  as  I  have  already  pointed  out,  a  matter  which 
requires  to  be  determined  by  future  observation.  It  is  one  of  the 
facts  which  require  to  be  settled  before  we  can  come  to  a  definite 
conclusion  as  to  whether  the  condition  which  we  term  pernicious 
anaemia  is  a  definite  and  distinct  disease,  or  whether  it  is  a  clinical 
condition  which  may  result  from  a  variety  of  morbid  lesions,  or 
rather  of  different  causes. 

Prognosis. 

The  prognosis  of  pernicious  anaemia  is  always  very  grave. 
Many  cases  steadily  progress  in  spite  of  treatment,  and  the  vast 
majority  of  cases  ultimately  terminate  in  death.  Until  the  year 
1875,  when  I  first  employed  arsenic  in  the  treatment  of  the  disease, 


PERNICIOUS   AN/EMIA.  95 

no  known  method  of  treatment  seemed  to  be  attended  with  even 
temporary  benefit,  at  all  events  in  any  considerable  proportion  of 
cases,  though  in  isolated  instances  the  patients  had  got  well  under 
iron  and  phosphorus,  and  in  some  cases  which  had  been  diagnosed 
as  pernicious  anaemia  by  competent  authorities,  a  (?  temporary) 
cure  had  spontaneously  resulted,  i.e.,  without  any  treatment.  Up 
to  the  time  that  I  directed  attention  to  the  value  of  arsenic  in  the 
treatment  of  the  disease,  the  opinion  expressed  by  Addison  prac- 
tically represented  the  experience  of  all  clinical  observers  ;  and  as 
regards  the  ultimate  result,  that  opinion  probably  correctly  repre- 
sents the  experience  of  almost  all  physicians  at  the  present  time, 
provided  only  that  the  cases,  which  are  temporarily  relieved  and  appa- 
rently cured,  are  followed  up  and  watched  for  a  sufficiently  long  period 
of  time.  But  under  arsenical  treatment,  the  immediate  prognosis  is 
certainly  more  hopeful.  No  one  who  has  had  large  experience  of 
the  disease,  and  has  given  arsenic  a  fair  trial,  in  a  considerable  num- 
ber of  cases,  can  fail,  I  think,  to  have  come  to  the  conclusion  that 
some  cases  improve  in  the  most  remarkable  way  under  the  admin- 
istration of  large  doses  of  the  drug.  Many  independent  observers 
have  published  cases  in  which  the  results  of  the  arsenical  treatment 
were  markedly  beneficial.* 

In  some  cases,  the  improvement  which  follows  the  administra- 
tion of  arsenic  is  so  marked  and  rapid  that,  in  them,  the  remedy 
seems  almost  to  be  a  (temporary)  specific  ;  in  other  cases,  arsenic 
produces  little  or  no  benefit.  I  have  used  the  term  temporary 
specific  advisedly,  for  as  Dr  Hale-White  has  pointed  out,  in  the  vast 
majority  of  the  cases  which  are  temporarily  relieved  and  it  may  be 
for  the  time  apparently  cured  by  arsenic  (and  I  may  add  by  every 
other  plan  of  treatment  which  has  as  yet  been  employed),  a  relapse 
subsequently  occurs  and  the  disease  ultimately  proves  fatal.  This 
at  all  events  represents  my  own  experience.  A  tendency  to  relapse 
is  one  of  the  most  striking  features  of  the  disease.  In  this  respect 
pernicious  anaemia  closely  resembles  chlorosis  ;  but  while  in  chlorosis 
the  natural  tendency  in  all,  or  almost  all,  uncomplicated  cases  is 

*  The  following  amongst  others  in  this  country  have  reported  cases  success- 
fully treated  by  arsenic  : — Byrom  Bramvvell,  "  Ed.  Med.  Journ.,"  1877,  and 
"Lancet,"  1897  ;  Lockie,  "  British  Medical  Journal,"  1878  ;  Stephen  Mackenzie, 
"Lancet,"  1879;  Finny,  "British  Medical  Journal,"  1880;  Broadbent,  "British 
Medical  Journal,"  1880  ;  Mitchinson,  "  Lancet,"  1881  ;  Withers  Moore,  "  British 
Medical  Journal,"  1881  ;  Pye-Smith,  "Guy's  Hosp.  Rep.  xxvi.  (New  Series)," 
1882;  Padley,  "Lancet,"  1883;  Willcocks,  "Practitioner,"  1883;  Wilks, 
"Lancet,"  1885  ;  Hale- White,  "Guy's  Hosp.  Rep.,"  1890;  Handford,  "British 
Medical  Journal,"  1891  ;  Risien  Russell,  "British  Medical  Journal,"  1894  ;  &c. 


g6  DISEASES  OF   THE   BLOOD. 

towards  recovery  and  spontaneous  cure,  in  pernicious  anaemia  the 
very  reverse  is  the  case — the  natural  tendency  in  all  cases  seems 
to  be  towards  relapse  and  death. 

It  remains  for  future  observation  to  show  whether  relapses  can 
be  prevented  by  the  continued  administration  of  arsenic  or  of  bone- 
marrow  (for,  as  I  will  presently  point  out,  bone-marrow  appears  to 
be  beneficial  in  some  cases  of  the  disease),  and  by  minute  attention 
to  the  general  health,  to  the  hygienic  surroundings,  and  to  the  con- 
dition of  the  gastro-intestinal  tract.  I  am  not  without  hope  that 
this  may  be  the  case. 

Immediate  prognosis. — In  cases  of  pernicious  anaemia  the 
immediate  prognosis  largely,  of  course,  depends  upon  the  severity  of 
the  individual  case — and  this,  when  the  patient  first  comes  under 
notice  {i.e.,  before  the  effects  of  treatment  can  be  taken  into  account), 
must  be  chiefly  judged  of  by  the  degree  of  the  ancsmia  and  the  exact 
diameters  of  the  blood  changes  which  are  present,  and  by  t lie  severity 
of  the  general  {constitutional}  symptoms. 

The  disease  is  almost  always  rapidly  fatal  in  cases  in  which 
the  number  of  blood  corpuscles  sinks  below  600,000  per  c.mm.  ; 
though  in  one  remarkable  case  reported  by  Quincke  in  which  the 
red  corpuscles  are  said  to  have  numbered  only  143,000  per  c.mm., 
the  patient  recovered  under  the  transfusion  of  185  c.c.  of  defibrinated 
blood.  It  is  worthy  of  note,  and  confirmatory  of  Dr  Stephen 
Mackenzie's  statement  that  Quincke's  figures  read  low,  that  in  this 
case,  on  recovery,  the  red  corpuscles  are  said  to  have  numbered 
only  1,234,000  per  c.mm. 

Cabot  thinks  that  the  microscopic  characters  of  the  blood  are  of 
importance  for  the  purposes  of  prognosis.  He  states  that  although 
"  the  prognosis  is  always  bad,  the  following  scheme  indicates  the 
presence  of  a  severe  or  of  a  mild  type  of  the  disease  : — 

"  1.  Severe  {rapidly  fatal).  2.  Less  Severe  {sloiver  course), 

{a.)  Extreme    progressive  (a.)  Remissions. 

anaemia. 

(b.)  High-colour  index.  (b>)  Normal  or  low-colour  index. 

\c.)   Increase  in  size  of  red  cells.  (c.)   Normal-sized  cells. 

{d.)  Degenerative  changes.  (d.)  No  degenerative  change. 

(*.)   Numerous  megaloblasts.  (e.)  Few  megaloblasts. 

(/)  Few  or  no  normoblasts.  (/)  Numerous  normoblasts. 

(g.)  Lymphocytosis.  CfO  Normal  percentage  of  adult 

cells."* 

*  "Clinical  Examination  of  the  Blood,"  p.  131 


PERNICIOUS   ANEMIA.  97 

While  these  conclusions  no  doubt  hold  true  in  most  cases,  it 
must  be  remembered  that  exceptions  to  them  occur.  Thus,  in 
a  remarkable  case  in  which  pernicious  anaemia  and  Addison's 
disease  appeared  to  be  combined,  although  the  red  corpuscles  only 
numbered  450,000  per  c.mm.  (with  one  exception  the  lowest  number 
which  I  have  personally  observed  in  any  case)  there  was  little  altera- 
tion in  the  size  of  the  red  corpuscles  and  comparatively  little 
poikilocytosis.  In  that  case,  too,  the  haemoglobin  was  very  greatly 
reduced,  indeed  more  reduced  than  the  red  corpuscles  (the  colour 
index  was  only  .55).  It  should,  however,  be  noted  that  the 
diagnosis  in  this  case  was  attended  with  difficulty  ;  the  condition 
seems  to  have  been  originally  chlorosis  and  ulceration  of  the 
stomach,  and  even  in  its  later  stages  the  colour  index  and  char- 
acters of  the  blood  were  more  suggestive  of  chlorosis  than  of 
pernicious  anaemia  (see  Abstract,  Case  31). 

The  length  of  time  that  the  disease  has  existed  and  the  stage  at 
which  it  comes  under  treatment  are  also  very  important  points  so 
far  as  the  immediate  prognosis  is  concerned  ;  for,  in  the  later  stages 
of  aggravated  cases  arsenic  is,  as  a  rule,  useless,  though  this  is  not 
invariably  the  case. 

I  am  disposed  to  think  that,  in  those  cases  in  which  the  disease 
is  of  short  duration  and  in  those  cases  in  which  it  is  rapidly 
developed,  arsenic  is  more  likely  to  be  beneficial,  and  the  prognosis 
consequently  somewhat  more  favourable,  than  in  the  chronic  and 
old-standing  cases  ;  but  I  speak  with  reserve  on  this  point. 

Many  of  the  cases  of  pernicious  anaemia  which  have  come 
under  my  notice  of  recent  years  were  seen  once  only  in  consultation, 
some  of  them  only  a  short  time  before  the  fatal  termination  took 
place — in  some  of  them,  the  disease  was  in  such  an  advanced  stage 
that  recovery  could  not  be  expected  under  any  plan  of  treatment. 

Repeated  relapses  are  unfavourable  indications  ;  in  all  of  my 
cases  in  which  more  than  one  relapse  occurred,  the  patients 
ultimately  died.  My  experience  goes  to  show  that  arsenic  has  a 
less  beneficial  influence  upon  the  relapses  than  upon  the  original 
attack. 

The  age  of  the  patient. — Whether  the  prognosis  is  more  favour- 
able in  young  subjects  than  in  middle-aged  adults  and  old  people, 
I  am  unable  to  say. 

The  patients  ability  to  take  arsenic  in  sufficient  (full )  doses  is  a 
most  important  (personally  I  am  disposed  to  think  the  most 
important)  point.  This  is  very  clearly  brought  out  in  the  analysis 
of  the  results  of  treatment  in  my  45  cases.  I  will  refer  to  this 
point  in  more  detail  presently. 

G 


98  DISEASES   OF   THE   BLOOD. 

Provided  that  the  case  is  not  too  far  advanced,  that  it  is  not  of 
too  long  duration,  and  that  large  doses  of  arsenic  are  well  borne, 
there  is  in  many  cases  a  reasonable  hope  of  marked  temporary 
improvement  or  complete  temporary  recovery. 

The  immediate  prognosis  is  always  very  grave  in  those  cases 
in  which  hemorrhages  (other  than  retinal  haemorrhages)  occur ; 
epistaxis,  in  some  cases,  should  also  perhaps  be  excepted;  but  in 
my  own  cases  epistaxis  was  usually  a  late  symptom. 

The  frequent  recurrence  of  febrile  attacks  with  jaundice  and  dark- 
coloured  urine  is  also  I  think  unfavourable,  since  these  conditions 
are  indicative  of  exacerbations  of  the  blood  destruction  which  is 
the  fundamental  feature  of  the  disease.  But  too  much  importance 
must  not  be  attached  to  this  point.  In  the  case  in  my  series 
(Case  26)  in  which  jaundice  was  most  marked,  the  beneficial  effect 
of  arsenic  was  perhaps  greater  than  in  any  other  Again,  in 
Case  40,  in  which  the  urine  was  persistently  very  dark  in  colour 
and  the  symptoms  most  profound,  though  the  patient  ultimately 
relapsed  and  died,  he  improved  for  a  time  in  a  very  marked  degree 
under  large  doses  of  the  remedy. 

The  presence  of  obstinate  and  intractable  diarrhoea  is  also  in  most 
cases  unfavourable.  Profound  nervous  symptoms,  such  as  extreme 
restlessness,  delirium,  semi-coma,  convulsions,  or  coma,  are  of  the 
gravest  significance;  such  symptoms  are  usually  the  immediate 
precursors  of  death. 

To  sum  up,  in  trying  to  form  an  immediate  prognosis  in  cases 
of  pernicious  anaemia  attention  should  be  chiefly  directed  to  the 
following  points  : — The  degree  of  the  anaemia  ;  the  exact  character 
of  the  blood  (colour  index  and  microscopic  characters)  ;  the  severity 
of  the  general  constitutional  symptoms  (debility,  dropsy,  etc.) ;  the 
length  of  time  which  the  disease  has  continued  ;  the  patient's 
ability  to  take  arsenic  in  large  doses  for  long  periods  of  time  ;  and 
the  presence  or  absence  of  grave  symptoms  and  of  complications, 
such  as  severe  and  obstinate  diarrhoea,  haemorrhages,  nervous 
symptoms,  etc. 

Ultimate  prognosis. — As  regards  the  ultimate  prognosis,  my 
experience  shows  only  too  clearly  that  in  the  vast  majority  of  cases, 
even  in  those  in  which  a  complete  cure  seems  for  the  time  to  have 
resulted  from  arsenical  treatment,  a  relapse  sooner  or  later  occurs, 
and  death  ultimately  takes  place.  But  I  repeat  that  I  am  not 
without  hope  that  if  arsenic  is  steadily  given  for  long  periods  of 
time  after  (temporary)  recovery,  the  tendency  to  relapse  which  is 
such  a  striking  feature  of  the  disease  may  perhaps  be  prevented. 

In  one  of  my  cases  the  patient  remained  well  for  12  years  and 


PERNICIOUS   ANEMIA.  99 

then  relapsed  and  died  from  the  disease  (13!  years  after  the  first 
attack).  In  no  other  of  my  cases,  in  which  the  result  is  known, 
has  the  patient  lived  more  than  3  years  after  he  first  came  under 
observation  ;  in  one  case  death  was  due  to  an  intercurrent  attack 
of  pneumonia — not  directly  at  all  events  to  pernicious  anaemia  ; 
in  three  cases  only,  in  which  the  ultimate  result  of  the  treatment  is 
known,  do  the  patients  still  survive  ;  two  of  them  are  in  good 
health. 

Treatment. 

So  far  as  my  own  experience  is  concerned — and  I  think  I  may 
correctly  say  that  the  experience  of  most  other  observers  is  entirely 
corroborative  of  it — the  only  remedy  with  which  we  are  at  present 
acquainted  which  is  likely  to  produce  benefit,  in  any  considerable 
proportion  of  cases  of  pernicious  anaemia,  is  arsenic. 

I  was  led  to  try  the  administration  of  arsenic  in  pernicious 
anaemia  by  the  following  chain  of  reasoning  : — I  knew  from  patho- 
logical observation  that  in  cases  of  pernicious  anaemia  the  most 
striking  naked-eye  appearance  was  the  extreme  fatty  degenera- 
tion of  the  heart.  I  further  knew  that  arsenic  was  a  remedy  of 
undoubted  value  in  the  treatment  of  many  cases  of  fatty  heart. 
I  consequently  said  to  myself,  Why  not  try  the  effect  of  arsenic  in 
pernicious  anaemia  ?  I  happened  about  this  time  to  have  several 
cases  of  pernicious  anaemia  under  my  care  in  the  Newcastle 
Infirmary.  In  three  of  the  cases  in  which  I  first  tried  the  remedy, 
rapid  and  immediate  improvement  took  place  ;  and  the  result  of 
my  whole  experience,  which  now  extends  over  twenty-three  years, 
goes  to  show  that  the  arsenical  treatment  is  in  many  cases  attended, 
for  a  time  at  least,  with  marked  benefit. 

Unfortunately,  as  I  have  just  pointed  out,  the  beneficial  effects 
of  arsenic  are  in  the  vast  majority  of  cases  only  temporary.  But 
instead  of  merely  making  general  statements  I  will  now  describe 
in  detail  the  results  of  the  treatment  in  the  45  cases  which  have 
come  under  my  own  notice.  These  results  are  particularly  valuable 
since  the  number  of  cases  is  large,  and  especially  since  they  have,  with 
few  (seven)  exceptions,  been  followed  to  their  ultimate  termination. 

The  results  of  the  treatment  in  all  of  the  45  cases  of  pernicious 
anaemia  which  have  come  under  my  own  observation  are  detailed 
in  Table  6  and  in  the  following  analysis.  I  append  to  this  paper 
an  Abstract  of  the  chief  clinical  and  pathological  details  of  all  of 
these  cases.* 

*  Since  this  Analysis  and  Table  6  were  set  in  type,  I  have  met  with  three 
additional  cases  of  the  disease.  The  chief  facts  in  their  clinical  history  are 
detailed  below.     (See  Abstract,  Cases  46,  47,  and  48.) 


Table  6. — Showing  the  Results  of  Arsenical  Treatment  in 
45  Cases  of  Pernicious  Anaemia. 


<->■"  *. 

Maximum 

■j 

Sex. 

Treatment  Adopted. 

e  u  «J 

g  0  c 
C~  0 

<  -:J- 

Dose  in 

Drops  of 

Fowler's  Solu- 

Immediate Result. 

Subsequent 
Progress. 

Ultimate 
Result. 

Duration 
of  life  after 
first  seen. 

z 

-J. 

< 

43 

M  F 

^  S 

tion  Daily. 

1 

1 

Iron,  quinine,  cod-liver  oil,   lime 

w 

iS 

Complete    (?  tempo- 

Not known 

Not  known 

juice — without   improvement. 

rary)  recovery 

Then  arsenic 

- 

20 

1 

Arsenic 

w 

12 

Complete    (?  tempo- 
rary) recovery 

Not  known 

Not  known 

3 

34 

1 

Iron,  quinine,  lime  juice,  stimulants 

No  improvement 

Death 

14  days 

4 

-: 

1 

Quinine,  astringents,  and  stimul'nts 

No  improvement 

Death 

16  days 

3 

29 

1 

Iron,  astringents,  stimulants 

No  improvement 

Death 

12  days 

6 

3S 

1 

Iron,   quinine,   and   phosphorised 
cod-liver  oil  for  3  weeks,  with- 
out improvement.  Then  arsenic 

w 

48 

Complete  recovery 

Relapse  12  years 
after 

Death 

13 J  years 

- 

31 

1 

Arsenic  tried,  but  disagreed.    The 
carbonate  of  iron 

B 

6 

Complete    ('?  tempo- 
rary) recovery 

Not  known 

Not  known 

i 

47 

1 

None — would  not  remain  in  hospital 

No  change 

Not  known 

Not  known 

9 

'7 

1 

Arsenic,  iron,  q'nine,  &  stomachics 

w 

27 

No  improvement 

Death 

53  days 

i . 

51 

1 

Arsenic   (but  it  disagreed),   Beta- 
naphthol,  thymol 

B 

6 

No  improvement 

Death 

21  days 

1 1 

54 

1 

Arsenic 

Temp'rary  impr'vm't 

Relapse 

Death 

1  year 

i  j 

so 

1 

Arsenic 

B 

•> 

Not  known 

Not  known 

Not  known 

13 

3; 

1 

Arsenic 

W 

30 

Complete    (?  tempo- 
rary) recovery 

Relapse  1  year 
after 

Death  t 

15  month 

:4 

41 

1 

Arsenic 

w 

42 

Rapid  disappear'nee 
of  anaemia 

Relapse  (abscess 
of  kidney) 

Death  t 

4  months 

15 

42 

1 

Arsenic  and  iron 

w 

3° 

Complete    (?  tempo- 
rary) recovery 

Relapse   1  year 
after 

Death 

18  months 

16 

53 

1 

Arsenic  and  iron 

w 

18 

Marked   and    rapid 

Relapse     when 

Death  § 

2  years 

improvement 

arsenic  discontinued 

17 

54 

1 

Arsenic  and  iron 

w 

15 

Marked    temporary 
improvement 

Relapse  9  mths. 
after 

Death 

18  months 

18 

62 

1 

Arsenic 

? 

•) 

Marked  impr'veinn't 

Not  known 

Not  known 

19 

63 

1 

Arsenic  and  bone-marrow  advised, 
but  would  not  take 

0 

0 

Death 

2  days 

20 

53 

1 

Arsenic  and  iron 

w 

20 

Decided   temporary 
improvement 

Relapse  4  months 
after,  and  arsenic 
not  subsequently 
given 

Death 

5  months 

2] 

31 

1 

Arsenic 

w 

12 

Marked  impr'v'm'nt 

Relapse  n  mths. 
after 

Death 

16  months 

12 

66 

1 

Arsenic    (could    only    take   small 
doses)  and  bone-marrow 

B 

9  (for  a  few 
days) 

No  improvement 

Death 

3  weeks 

-; 

57 

1 

Arsenic    (could    only    take   small 
doses),  iron  (it  disagreed)  and 
salicylate  of  bismuth 

B 

6 

No  improvement 

Death 

2  months 

-4 

4- 

1 

Arsenic,  and  after  relapse  arsenic 

w 

36 

Temporary  recovery 

Relapse  9  mths. 

Death 

17  months 

and  bone-marrow 

after;  again  recovered  under 
arsenic.     Second  relapse   5 
months  later 

-3 

54 

1 

Arsenic 

w 

42 

Slight  temporary  im- 
provement 

Death 

5  months 

:-- 

53 

1 

Arsenic 

w 

60 

Complete  (?  tempo- 
rary) recovery 

Slight  relapse  10 
months  after 

Well 

1  year 

-7 

5- 

1 

Arsenic 

w 

57 

Very  slight  improve- 
ment 

Not  known 

Not  known 

2 1 

5-: 

1 

Arsenic 

w 

60 

Complete    (?  tempo- 
rary) recovery 

Remains  well 

Well 

1  year 

29 

49 

1 

Arsenic  and  salicylate  of  bismuth 

B 

9  (for  a  few 
days  only) 

No  improvement 

Death 

4  months 

3 

4- 

t 

Arsenic  advised— could  not  take 

B 

9  (for  a  few 
day  s  only) 

No  improvement 

Death 

11  days 

31 

16 

1 

Arsenic  and  iron 

B 

12     (for     a 
short  time) 

No  improvement 

Death 

2  months 

32 

41 

1 

Arsenic  and  iron 

W 

24 

Complete  temporary 

Relapse  10  mths. 

Death 

2j  years 

recovery 

after  ;  again  improved  with 
arsenic.     Second  relapse  5 
mths.  later;  again  improved. 
Third  relapse  6  mths.  later. 

33 

54 

1 

Arsenic.      After    relapse,    arsenic 
and  bone-marrow 

w 

40 

Complete  temporary 
recovery 

Relapse     a      year 
after ;  again  im- 
proved under  ar- 
senic.     Second 
relapse 

Death 

2  years 

34 

46 

1 

Arsenic,  iron  and  bone-marrow 

w 

45 

Slighttemporary  im- 
provement 

Death 

3  months 

35 

72 

1 

Arsenic 

9 

? 

Slight  tern,  improve. 

Death 

3  months 

36 

5° 

1 

Arsenic  and  iron  advised — patient 
refused  to  take 

0 

0 

No  improvement 

Death 

1  month 

37 

7' 

1 

Arsenic 

? 

Marked    temporary 
improvement 

Relapse  5  mths. 
later 

Death 

8  months 

3? 

58 

1 

Arsenic  and  iron 

•> 

1 

Temporary  improve- 
ment 

Relapse 

Death 

1  year 

3 

•■; 

1 

Arsenic  and  salicylate  of  bismuth 

B 

9  (for  a  few 
days  only) 

No  improvement 

Death 

1  month 

■V 

7 

1 

Arsenic  and  salicylate  of  bismuth 

\V 

63 

Marked    temporary 
improvement 

Relapse 

Death 

4  months 

41 

5' 

1 

Arsenic,  strychnine,  &c. 

w 

15 

No  improvement 

Death 

8  days 

45 

3' 

1 

Arsenic,       oxygen       inhalations, 
strychnine  and  digitalis 

w 

30 

No  improvement 

Death 

5  days 

4 

6S 

1 

Arsenic,  bone-marrow,  transfusion 

RTus'd 
to  take 

5 

Slight  improvement 
(transfusion) 

In  statu  quo 

6  months 

4 

it 

1 

Arsenic,  bone-marrow,  oxygen  in- 
halations, strychnine,  &c. 

W 

45 

Slight  temporary  im- 
provement 

Death 

6  weeks 

•'- 

3'- 

1 

j  Arsenic,  oxygen  inhalations,  &c. 

W 

42 

No  improvement 

Death 

18  days 

W  =  well  borne  :    B  =  badly  borne. 


t  Immediate  cause,  cerebral  haemorrhage. 
§  Pneumonia. 


J  Abscess  of  kidney  found  post  mortem. 


PERNICIOUS   ANEMIA.  IOI 


Analysis  of  the  Results  of  Treatment  in  45  Cases  of 
Pernicious  Anaemia. 

Cases  in  which  arsenic  was  not  given. — In  seven  of  the  forty-five  cases,  no 
arsenic  was  given  (Cases  3,  4,  5,  8,  19,  36  and  43).  In  four  of  these  cases  (3,  4,  5 
and  8)  arsenic  was  not  prescribed  ;  these  patients  came  under  my  notice  before  I 
appreciated  the  value  of  arsenic  in  the  treatment  of  the  disease.  In  the  remain- 
ing three  cases  (19,  36  and  43),  arsenic  was  prescribed,  but  the  patients  refused 
to  take  it. 

In  five  of  the  seven  cases  in  which  no  arsenic  was  given,  the  patients  died 
within  a  month,  and  usually  much  sooner,  namely,  in  14,  16,  12,  2  and  ^o  days 
respectively.  In  one  of  the  remaining  cases,  the  patient  refused  to  stay  in 
hospital  and  submit  himself  to  treatment ;  the  ultimate  result  in  that  case  is 
not  known.  In  the  other  case  (43),  there  was  some  improvement  under 
transfusion. 

Cases  in  which  arsenic  was  administered. — In  thirty-eight  of  the  forty-five 
cases,  arsenic  was  given. 

In  ten  of  these  cases  (1,  2,  6,  13,  15,  24,  26,  28,  32  and  33),  complete  (tem- 
porary) recovery  resulted  ;  in  eight  (14,  16,  17,  18,  20,  21,  37  and  40),  there  was 
marked  temporary  improvement ;  in  seven  (11,  25,  27,  34,  35,  38  and  44),  there 
was  slight  temporary  improveme?it ;  in  twelve  cases  (7,  9,  10,  22,  23,  29,  30,  31, 
39,  41,  42  and  45),  there  was  no  improvement j  (in  one  of  these  cases — 7 — in 
which  arsenic  disagreed  and  was  discontinued  the  patient  recovered  under 
carbonate  of  iron  ;  in  another — 43 — there  was  some  improvement  under  trans- 
fusion) ;  and  in  one  case  (12)  the  result  is  not  known. 

Thus  in  twenty-five  out  of  thirty-eight  cases  in  which  arsenic  was  administered 
there  was  more  or  less  improvement  ;  in  seven  the  improvement  was  slight,  in 
eight  marked,  and  in  ten  there  was  complete  (temporary)  recovery. 

Ultimate  result  in  the  cases  in  which  complete  temporary  recovery  took 
place. — In  seven  of  the  ten  cases  in  which  complete  (temporary)  recovery  resulted, 
a  relapse  subsequently  occurred  (Cases  6,  13,  15,  25,  26,  32  and  33) ;  in  one  (28), 
there  has  been  no  relapse  and  the  patient  remains  well  (one  year  after  the  treat- 
ment was  commenced) ;  in  the  remaining  two  cases  (1  and  2),  the  result  is 
tiftknown. 

In  six  of  the  seven  cases  in  which  a  relapse  occurred,  the  patients  have  died 
(6,  13,  15,  24,  32  and  33)  ;  in  one  case  (26),  the  patient  has  again  completely 
recovered,  for  the  time,  under  arsenic. 

In  the  seven  cases  which  completely  recovered  for  a  time  and  then  relapsed 
and  died,  in  one  case  (6)  the  patient  remained  well  for  12  years  and  died  at  the 
end  of  13!  years  ;  in  all  the  other  cases  (13,  15,  24,  26,  32  and  33),  a  relapse 
occurred  within  a  year  (the  exact  date  of  occurrence  of  the  relapse  is  given  in 
Table  5). 

In  seven  of  the  eight  cases  in  which  there  was  marked  improvement  but  not 
complete  (temporary)  recovery  under  the  treatment,  death  ultimately  occurred  ; 
and  in  the  remaining  case  (18),  the  ultimate  result  is  not  known. 

In  the  seven  cases  in  which  there  was  slight  improvement,  six  died  (Cases 
11,  25,  34,  35,  38  and  44) ;  and  in  one  case  (27),  the  result  is  not  known. 


An  analysis  of  the  immediate  results  of  the  treatment  in  those  cases  in  which 
arsenic  was  well  and   badly  borne  shows  very  clearly  that   the  prospect   of 


102  DISEASES   OF   THE   BLOOD. 

immediate  improvement  under  this  treatment  largely  depends  upon  the  patient's 
ability  to  take  full  doses  of  the  drug.     The  analysis  is  as  follows  : — 

Results  of  the  treatment  in  those  cases  in  which  arsenic  was  well  borne. — 
In  the  total  number  of  thirty-eight  cases  in  which  arsenic  was  given,  the  remedy 
was  well  borne  in  twenty-four  cases. 

The  results  of  the  treatment  in  these  twenty-four  cases  was  as  follows : — In  ten, 
there  was  complete  (temporary)  recovery  (Cases  i,  2,6,  13,  15,  24,  26,  28,  32  and 
^)  ;  in  six,  there  was  marked  temporary  improvement  (Cases  14,  16,  17,  20,  21 
and  40) ;  in  four,  there  was  slight  temporary  improvement  (Cases  25,  27,  32  and 
44);  and  in  four,  there  was  no  improvement  (Cases  9,  41,  42  and  45). 

The  maximum  dose  of  arsenic  which  each  of  these  patients  was  able  to  take 
per  diem  was  as  follows  : — 

Cases  which  completely  recovered. — Case  1  =  18  drops;  Case  2  =  12  drops; 
Case  6  =  48  drops  ;  Case  1 3  =  30  drops  ;  Case  1 5  =  30  drops  ;  Case  24  =  36  drops  ; 
Case  26  =  60  drops;  Case  28  =  60  drops;  Case  32  =  24  drops;  Case  33  =  40 
drops. 

Cases  in  which  there  was  marked  improvement. — Case  14  =  42  drops  ;  Case 
16=18  drops;  Case  17  =  10  drops;  Case  20  =  20  drops;  Case  21  =  12  drops; 
Case  40  =  63  drops. 

Cases  in  which  there  was  slight  improvement. — Case  25=42  drops;  Case 
27  =  57  drops  ;  Case  34  =  45  drops  ;  Case  44  =  45  drops. 

Cases  in  which  there  was  no  improvement. — Case  9  =  27  drops  ;  Case  41  =  15 
drops;  Case  42  =  30  drops  (this  patient  died  five  days  after  commencing  the 
treatment) ;  and  Case  45  =  42  drops. 

Results  of  the  treatment  in  those  cases  in  which  arsenic  was  badly  borne.— 
In  the  total  thirty-eight  cases  in  which  arsenic  was  given,  it  was  badly  borne  in 
nine  cases. 

The  results  of  the  treatment  in  these  nine  cases  was  as  follows  : — Complete 
recovery  in  one  case  (7)  under  carbonate  of  iron  after  arsenic  had  failed  ;  no  im- 
provement in  seven  cases,  namely,  10,  22,  23,  29,  30,  31  and  39  ;  and  the  result 
not  known  in  one  case  (12). 

Results  of  the  treatment  in  those  cases  in  which  the  dose  of  arsenic  is  not 
known.  —  In  the  remaining  five  of  the  total  number  of  thirty-four  cases  in  which 
arsenic  was  given,  I  am  unable  to  state  whether  the  remedy  was  well  or  ill  borne, 
or  to  give  the  maximum  dose  which  the  patient  took. 

The  result  in  these  five  cases  was  as  follows  : — Marked  temporary  improve- 
ment in  two  cases  (18  and  37);  slight  temporary  improvement  in  three  cases 
(11,  35  and  38). 

Summary. 

The  immediate  and  ultimate  result  of  the  treatment  in  the  45  cases  included 
in  Table  6  is  therefore  as  follows  : — 

Ultimate  Result  in  45  Cases  of  Pernicious  Anaemia  under  Various  Plans  of 

Treatment. 

In  good  health  at  present  time  -  -  2  cases. 

Still  under  treatment  -  -  -  -  1      ,, 

Dead  -  35      „ 

Result  not  known      ...  •  7      n 

Total  45      „ 


PERNICIOUS   ANEMIA.  103 

Immediate  Result  in  45  Cases  of  Pernicious  Anaemia  under  Various  Plans  of 

Treatment.      ' 

Complete  (temporary)  recovery        -             -  10  cases. 

Marked  (temporary)  improvement    -  8      ,, 

Slight  (temporary)  improvement       -  8      „ 

No  improvement        -                                       -  17      ,, 

Immediate  result  not  known  -             2      „ 

Total  45      „ 

Immediate  Result  in  7  Cases  not  Treated  with  Arsenic. 

No  improvement       -----  5  cases. 

Slight  temporary  improvement          -             -  -             1      „ 

Result  not  known      -             -             -             -  -             1      „ 

Total  7      „ 

Immediate  Result  in  38  Cases  Treated  with  Arsenic. 

Complete  (?  temporary)  recovery 

No  relapse  - 

Relapse  and  recovery     - 

Relapse  and  death  - 

Marked  (temporary)  improvement    - 
Slight  (temporary)  improvement 
No  improvement        - 
Result  not  known      - 

Total  -           38      „ 

Immediate  Result  in  the  24  Cases  in  which  Arsenic  was  Well  Borne. 

Complete  recovery     -                          -  -           10  cases. 

With  no  relapse  1 

With  relapse  and  recovery         -             -  1 

With  relapse  and  death              -  6 

Result  unknown              -             -             -  2 

Marked  (temporary)  improvement    -  6      ., 

Slight  (temporary)  improvement       -  4      „ 

No  improvement        -             -             -             -  -             4      ,, 

Total             -  -           24      „ 

Immediate  Result  in  the  9  Cases  in  which  Arsenic  was  Badly  Borne. 

Complete  (?  temporary)  recovery  (under  iron)  -             1  case. 

No  improvement        -  7     j> 

Result  not  known      -  1     „ 

Total             -  9     „ 

Immediate  Result  in  the  5  Cases  in  which  the  Dose  of  Arsenic  is  Not  Known. 

Marked  temporary  improvement  2  cases. 

Slight  temporary  improvement         -  3      „ 

Total             -  -             5      „ 


10  cases. 

I 

I 

Q 

O 

8      ., 

- 

7      „ 

- 

12      „ 

- 

1      „ 

104  DISEASES   OF   THE   BLOOD. 

General  treatment. — Before  referring  to  the  dose  of  arsenic 
and  the  mode  of  administration,  let  me  say  a  few  words  with  regard 
to  the  general  treatment  of  the  disease  ;  for  in  this  form  of  anaemia, 
as  in  chlorosis,  attention  to  the  hygienic  surroundings  and  the 
feeding  of  the  patient  are  of  great  importance. 

It  is  essential,  I  think,  that  the  patient  should  be  kept  at  abso- 
lute rest  in  bed,  or  at  all  events  in  the  recumbent  position,  until 
recovery  is  well  advanced.  I  attach  the  greatest  importance  to  this 
point.  It  is,  I  think,  one  of  the  reasons  why  advanced  cases  of  the 
disease  are  more  successfully  treated  in  hospital  than  in  private 
practice. 

The  patient  should  have  plenty  of  fresh  air  and,  if  possible,  an 
abundance  of  sunlight. 

The  diet  should  be  light  and  nutritious.  Owing  to  the  impaired 
digestive  power  of  the  stomach,  the  patient  is  usually  unable  to 
digest  solid  food.  Milk  and  milk  foods,  meat  extracts  (of  which 
Wyeth's  is  perhaps  the  best),  raw  beef  juice,  finely  grated  and 
pounded  raw  meat,  and  whipped-up  eggs  should  form  the  basis  of 
the  dietary.  On  the  view  that  pernicious  anaemia  is  the  result  of 
blood  destruction  in  the  portal  circulation  and  that  the  individual 
red  corpuscles  contain  more  than  the  normal  amount  of  haemo- 
globin, a  milk  diet  should  theoretically  be  preferable  to  a  red  meat 
diet ;  but  I  have  not  been  able  to  satisfy  myself  that  the  adminis- 
tration of  meat  extracts,  beef  juice,  or  pounded  raw  meat  is  harm- 
ful. On  the  contrary,  I  am  disposed  to  think  that  a  meat  diet  is  in 
some  cases  beneficial. 

The  condition  of  the  bowels  must  be  carefully  regulated.  If 
there  is  constipation — but  this  is  rare — gentle  laxatives  should  be 
given  ;  aloin,  cascara  and  sulphur  are  probably  the  best.  If  there 
is  diarrhoea,  it  should  be  arrested  as  soon  as  possible  ;  salicylate  of 
bismuth  is  one  of  the  best  remedies  for  this  purpose.  When  there 
is  reason  to  suppose  that  excessive  decomposition  is  going  on  in 
the  intestine,  intestinal  antiseptics  (Beta-naphthol,  thymol,  menthol 
or  salol)  may  be  tried  ;  thymol,  one  grain  three  times  a  day,  is 
perhaps  the  most  effective. 

It  is  unnecessary  to  say  that  in  those  cases  in  which  the  patient 
is  losing  blood  from  the  uterus,  piles,  etc.,  the  haemorrhage  should 
be  arrested  as  speedily  as  possible. 

In  rickety  children  who  are  suffering  from  profound  anaemia 
fwhich  it  is  sometimes  difficult  to  distinguish  from  pernicious 
anaemia),  the  appropriate  treatment  for  rickets  is  of  course  essen- 
tial, and  arsenic  and  iron  may  at  the  same  time  be  given. 
These  cases  can  hardly,  however,  be  included  under  the  term  per- 


PERNICIOUS   ANEMIA.  105 

nicious  anaemia,  though  the  blood  condition  is  very  similar,  so  far 
at  all  events  as  the  shape  and  size  of  the  red  blood  corpuscles  is 
concerned. 

Dose  and  Mode  of  Administration  of  Arsenic. — In  adminis- 
tering arsenic,  I  usually  begin  with  a  small  dose — two  drops  of 
Fowler's  solution  three  times  a  day,  given  in  plenty  of  water,  soon 
after  food.  I  gradually  increase  the  dose  by  one  drop  every  third 
day  (and  in  severe  and  advanced  cases  every  second  or  even  every 
day  unless  the  remedy  disagrees),  so  that  on  the  fourth  day  the 
patient  is  taking  three  drops,  on  the  seventh  day  four  drops,  on  the 
tenth  day  five  drops,  and  so  on.  Many  patients  affected  with 
pernicious  anaemia  can  ultimately  take  ten,  fifteen,  or  even  twenty 
drops  of  Fowler's  solution  three  times  daily.  In  two  of  my  cases, 
the  patients  took  as  much  as  sixty  drops  per  diem.  The  object  of 
the  treatment  is  to  gradually  increase  the  dose  until  the  maximum 
quantity  that  the  patient  can  take  without  any  discomfort  is 
reached.  When  the  patient  begins  to  complain  of  itching  of  the 
eyeballs,  pain  in  the  stomach  or  diarrhoea,  the  dose  should  be 
immediately  and  considerably  reduced  ;  subsequently  it  may  again 
be  increased  and  the  remedy  continued  in  the  largest  dose  which 
can  be  comfortably  and  satisfactorily  borne. 

The  long-continued  administration  of  arsenic  in  some  cases 
produces  pigmentation  of  the  skin,  and  in  others  peripheral  neuritis. 
I  have  observed  both  effects  in  a  few  cases. 

Many  patients  who  are  suffering  from  pernicious  anaemia  seem 
to  have  a  remarkable  tolerance  for  the  drug  ;  and  my  experience 
very  definitely  shows  that  it  is  precisely  in  those  cases  of  pernicious 
anaemia  (in  which  large  doses  of  arsenic  are  well  borne)  that  the 
remedy  is  most  likely  to  produce  benefit.  The  same  thing  is  seen 
in  many  other  diseases  in  which  a  remedy  is  markedly  beneficial  ; 
for  example,  iodide  of  potassium  in  syphilis,  opium  in  peritonitis, 
iron  in  chlorosis,  chloral  hydrate  in  some  cases  of  nervous  spasm,  etc. 

In  those  cases  in  which  the  arsenic  agrees  and  is  attended 
with  benefit,  it  should  be  steadily  continued  in  full  doses  until  the 
number  of  red  blood  corpuscles  reaches  the  normal,  and  until  the 
symptoms  of  the  disease  disappear. 

When  the  patient  is  apparently  cured,  the  dose  should  be 
reduced,  but  the  remedy  should  still  be  given  in  small  doses — three 
or  four  drops  of  Fowler's  solution  three  times  a  day — for  a  long 
period  of  time.  I  am  of  opinion  that  these  small  doses  should  be 
continued  for  several  months  at  least,  and  probably,  if  relapses 
are  to  be  prevented,  for  several  years.  I  attach  great  importance 
to  this  point,  and  I  am  hopeful  that  if  this  plan   of  treatment  is 


106  DISEASES   OF   THE   BLOOD. 

systematically  carried  out,  relapses  will  in  future  be  found  to  be 
less  common  than  they  have  been  in  the  past. 

Probable  Mode  of  Action  of  Arsenic. — The  exact  manner  in 
which  arsenic  produces  its  beneficial  effects  in  pernicious  anaemia 
is  not  yet  determined.  Dr  Hunter  suggests  that  it  probably  acts 
by  producing  a  healthier  condition  of  the  gastro-intestinal  tract, 
that  is  to  say  by  preventing  the  formation  and  absorption  of  the 
toxic  product  which  he  thinks  is  the  essential  cause  of  the  disease. 
Dr  Copeman  has  shown  that  under  the  administration  of  arsenic 
in  pernicious  anaemia,  the  haemoglobin  is  much  more  stable  ;  it 
does  not  tend  to  separate  from  the  corpuscles  after  withdrawal 
from  the  body  in  the  way  which  it  does  before  the  arsenic  was 
administered.  It  is  probable,  I  think,  that  the  remedy  acts 
both  in  the  manner  that  Dr  Hunter  has  suggested  and  as  a 
blood  tonic,  that  it  exerts  a  beneficial  effect  upon  the  bone- 
marrow,  enabling  the  marrow  to  form  healthier  red  blood  corpuscles 
— blood  corpuscles  which  are  more  resistant,  and  in  which  the 
haemoglobin  is  more  stable  and  intimately  combined.  But  be  this 
as  it  may.  the  beneficial  effect  of  the  remedy  in  many  cases  of  the 
disease  is  undoubted. 

Bone-marrow. — Professor  T.  R.  Fraser*  has  recommended  the 
administration  of  bone-marrow  and  has  published  a  case  in  which 
remarkable  improvement  occurred  under  the  combined  adminis- 
tration of  bone-marrow  and  arsenic.  He  concluded  that  in  that 
case  the  improvement  was  due  to  the  bone-marrow  rather  than  the 
arsenic  and  other  remedies  which  the  patient  was  taking.  It 
remains  to  be  seen  whether  further  observation  will  confirm  this 
opinion  or  not ;  and  it  is  only  right  to  state  that  (I  am  informed) 
in  that  case,  as  in  so  many  other  cases  of  pernicious  anaemia,  the 
disease  relapsed  and  the  patient  died  some  little  time  after  his 
discharge  from  hospital. 

Drs  Barrs  and  Danforth  have  also  published  cases,  and  I  have 
heard  of  some  other  cases  which  have  not  been  published,  in  which 
bone-marrow  was  beneficial  when  arsenic  had  failed.! 

So  far  as  present  experience  enables  us  to  judge,  bone-marrow 
appears  to  be  a  much  less  efficacious  remedy  than  arsenic. 
Further  information  is  required  before  it  is  possible  to  pronounce 
a  positive  opinion  as  to  the  value  of  bone-marrow  in  this  disease. 
Bone- marrow   has    not    appeared  to   produce  any  benefit  in   the 


*  "British  Medical  Journal,"  1894,  Vol.  i.,  p.  1172. 

f  "British    Medical   Journal,"    16th    February     1895;    "Chicago    Clinical 
Revue,"  October  1895. 


.      PERNICIOUS   ANAEMIA.  107 

cases  in  which  I  have  prescribed  it;  but  it  is  only  fair  to  say 
that  I  always  commence  the  treatment  with  arsenic,  and  that 
it  is  only  in  those  cases  in  which  arsenic  fails  to  produce  a 
(temporary)  cure — in  other  words,  marked  improvement — that  I 
prescribe  bone-marrow.  In  most  of  the  cases  in  which  I  have 
prescribed  bone-marrow,  it  has  in  the  course  of  a  short  time 
disagreed  with  the  stomach. 

Bone-marrow  is  perhaps  best  administered,  as  Dr  Lauder 
Brunton  has  pointed  out  to  me,  in  the  raw  state  mixed  with 
mashed  potato. 

Iron.  —  In  most  cases  of  true  pernicious  anaemia,  iron  usually 
fails  to  produce  any  beneficial  effect;  indeed,  in  some  cases  it 
seems  to  be  prejudicial.  But,  as  I  have  already  stated,  I  speak 
with  less  confidence  on  this  point  than  I  did  some  years  ago,  for 
in  some  of  my  recent  cases  most  marked  improvement  has  occurred 
under  the  simultaneous  administration  of  Robertson's  capsules 
together  with  large  and  gradually  increasing  doses  of  arsenic. 
Cases  have  however  been  reported  in  which  an  apparent  (?  tem- 
porary) cure  has  resulted  from  the  administration  of  iron  alone  *  ; 
and  Stockman  argues  that  if  a  case  of  pernicious  anaemia  is  curable 
at  all  (excluding  those  which  are  necessarily  fatal)  then  iron  is 
bound  to  be  of  value,  as  it  is  whenever  a  deficiency  of  haemoglobin 
has  to  be  made  good  f  ;  but  I  fail  to  follow  his  reasoning.  If  iron 
is  prescribed,  the  effects  of  the  remedy  should  be  very  carefully 
watched,  for  I  am  satisfied  (both  from  the  observation  of  my  first 
and  recent  cases)  that  in  some  cases  it  is  prejudicial  ;  in  a  recent 
case  the  patient  himself  volunteered  the  statement  that  it  did  harm 
and  increased  the  diarrhoea  which  in  his  case  was  a  prominent 
symptom. 

Intestinal  antiseptics. — Believing  that  the  disease  is  due  to 
the  absorption  of  a  poison  from  the  intestines,  Dr  Hunter  has 
recommended  the  administration  of  intestinal  antiseptics  (Beta- 
naphthol,  etc.) ;  Dr  George  Gibson  has  published  a  case  in  which 
this  plan  of  treatment  seemed  to  produce  a  remarkably  beneficial 
effect.  In  the  only  two  cases  in  which  I  have  tried  this  plan  of 
treatment,  no  improvement  resulted. 

Anthelmintics. — If  there  is  reason  to  suspect  the  presence  of 

*  Amongst  others,  the  following  cases  which  recovered  under  iron  have 
been  reported  : — Quincke  (Deut.  Archiv.,  Vol.  xx.,  p.  3) ;  Byrom  Bramwell  (Edin. 
Med.  Jour.,  Nov.  1877) ;  Wilks  (Lancet,  Vol.  i.,  1885,  p.  653) ;  Finlay  (Lancet, 
Vol.  i.,  1885,  p.  358). 

t  On  the  Nature  and  Treatment  of  Pernicious  Anaemia,  "  British  Medical 
Journal,"  May  4th,  nth,  and  18th,  1895. 


IOS  DISEASES   OF   THE   BLOOD. 

intestinal  worms  or  parasites  (and  in  all  cases  of  pernicious  anaemia 
the  faeces  should  be  examined  for  ova,  parasites,  etc.),  such  remedies 
as  thymol  or  santonin  should  be  given. 

Yellow  santonin,  a  remedy  which  has  recently  been  said  to  be  a 
specific  in  sprue,  in  which  disease  the  most  profound  anaemia  is 
sometimes  developed  (but  it  is,  so  far  as  my  experience  enables  me 
to  judge,  of  the  chlorotic  and  not  of  the  pernicious  type),  deserves, 
I  think,  a  thorough  trial  in  cases  of  this  kind,  and,  perhaps,  in 
all  cases  of  the  disease  in  which  the  diarrhoea  continues  and  the 
patient  does  not  improve  under  arsenic  and  salicylate  of  bismuth. 

Oxygen  inhalations  have  also  been  recommended.  I  have 
tried  the  remedy  in  a  few  cases  in  which  the  arsenic  and  bone- 
marrow  failed  to  produce  improvement,  but  without  any  beneficial 
result. 

Transfusion  of  blood  or  saline  solution  has  been  tried  by 
various  observers.  In  the  great  majority  of  cases  the  effect  was 
negative  or  prejudicial.  From  the  results  of  his  experimental 
observations  on  the  lower  animals,  Dr  Hunter  is  strongly  disposed 
to  think  that  transfusion  will  be  likely  to  do  more  harm  than  good. 
The  only  possible  effect  which,  in  his  opinion,  it  is  likely  to  produce 
is  temporary  benefit.  But  notwithstanding  these  theoretical  objec- 
tions, which  seem  to  be  based  on  satisfactory  reasoning,  good  results 
have  undoubtedly  been  obtained  in  a  few  cases.*  In  one  of  my 
cases  (a  private  patient)  in  which  blood  was  directly  transfused, 
a  very  temporary  rally  took  place,  but  the  patient  died  the  day 
after  the  operation  ;  in  another  case  in  which  the  patient  was 
unable  to  take  either  arsenic  or  bone-marrow,  decided  temporary 
improvement  has  resulted  from  transfusion.  This  case  is  still 
under  observation.     (See  Abstract,  Case  43.) 

If  further  observation  should  show  that  pernicious  anaemia  is  a 
clinical  condition  and  not  a  separate  disease  {i.e.,  if  pernicious 
anaemia  may  result  from  several  different  causes  and  not  merely 
from  one  cause),  it  is  reasonable  to  suppose  that  some  cases  will 
improve  under  one  remedy  and  some  under  another  (in  other 
words,  that  in  some  cases  arsenic,  in  others  bone-marrow,  will  be 
beneficial)  ;  and  if  this  should  be  the  case  it  is  not  unreasonable  to 
hope  that  further  observation  and  experience  may  enable  us  to 
differentiate  the  cases  in  which  arsenic,  bone-marrow  and  other 
remedies,  which  may  ultimately  be  employed  in  the  treatment  of 
the  disease,  are  most  beneficial. 


*  Quincke,  "  Deutsches   Archiv.,"    Vol.    xx.,    p.    1  ;    Brakenridge,  "  British 
Medical  Journal,"  1892  ;  Affleck,  "British  Medical  Journal,"  1892. 


PERNICIOUS   ANAEMIA,  109 

Let  me  repeat  that  in  the  advanced  stages  of  grave  cases  of 
pernicious  anaemia  it  is  unreasonable  to  expect  improvement  under 
any  of  our  present  plans  of  treatment,  though  exceptions  to  this 
statement  occasionally  occur. 

Cases  of  pernicious  anaemia  which  have  been  temporarily  cured 
by  arsenic  or  other  remedies  should,  as  I  have  already  stated,  be 
closely  and  continuously  watched.  The  blood  should  be  examined 
from  time  to  time.  If  any  indications  of  a  relapse  develop,  the 
dose  of  arsenic  should  be  immediately  increased.  The  tendency 
to  relapse  is  so  great  that  the  arsenic  should  be  continued  in  small 
doses  for  many  months  or  even  years  after  an  apparent  cure  has 
been  effected.  As  I  have  already  stated,  I  attach  the  greatest 
importance  to  this  point. 


Abstract  of  48  Cases  of  Pernicious  Anaemia  (Addison's 
Idiopathic  Anaemia)  Observed  by  the  Author  during 
Life. 

CASE  I. — Male,  aged  45,  cabman,  was  admitted  to  the  Newcastle  Infirmary 
on  18th  March  1875,  suffering  from  profound  anaemia  and  spinal 
symptoms. 

Duration. — 3  years. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  ;  loss  of  weight  ;  shortness  of  breath  and 
palpitation  on  exertion ;  red  corpuscles  much  diminished  in  number  ;  many  mega- 
locytes  and  microcytes  ;  marked  poikilocytosis  ;  some  excess  of  white  corpuscles  ; 
heart  sounds  weak  ;  soft  systolic  mitral  murmur  ;  area  of  cardiac  dulness  small  ; 
radial  pulse  56,  very  soft,  weak,  slightly  visible  and  jerking  ;  retinae  not  seen 
because  of  opacity  of  vitreous  ;  urine  normal  in  colour  ;  trace  of  albumen  ; 
numbness,  weakness  and  inco-ordination  in  arms  and  legs  ;  superficial  reflexes 
markedly  exaggerated. 

Treatment. — Iron,  quinine,  cod-liver  oil  and  lime  juice  were  at  first  pre- 
scribed ;  there  was  some,  but  only  slight,  improvement  ;  arsenic  was  then 
substituted  (maximum  dose,  18  drops  daily). 

Immediate  result. — Marked  and  rapid  improvement  under  arsenical  treat- 
ment ;  the  patient  was  discharged,  apparently  quite  well,  and  saying  he  was  fit 
for  work,  on  22nd  July  1875,  after  being  in  hospital  126  days. 

Subsequent  progress  and  Ultimate  result. — Not  known. 

Case  recorded  in  the  "  Edin.  Med.  Journal,"  Nov.  1877. 

CASE  II. — Male,   aged  20,   sailor,  admitted   to  the   Newcastle  Infirmary  on 
2 1  st  March  1875,  suffering  from  all  the  characteristic  symptoms  of  pro- 
found pernicious  anaemia. 
Duration. — 3  months. 

Apparent  cause. — An  attack  of  yellow  fever  four-and-a-half  months  pre- 
viously. 

Symptoms. — Profound  anaemia ;  great  weakness   and  prostration  ;  no  loss 


HO  DISEASES   OF   THE   BLOOD. 

of  weight  ;  shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles 
markedly  diminished  in  number;  many  megalocytes  and  microcytes ;  marked 
poikilocytosis  ;  apparent  nucleation  of  red  corpuscles  (colour  plate  of  blood 
published  in  "Edm.  Med.  Journal,"  Nov.  1877);  heart  of  normal  size;  soft 
systolic  mitral  murmur,  heard  also  in  other  areas  ;  pulse  112,  very  weak,  com- 
pressible and  visible  ;  retinal  haemorrhages  ;  epistaxis  ;  slight  dropsy  of  face  ; 
tongue  smooth,  clean  and  pale  ;  occasional  vomiting  ;  severe  diarrhoea  ; 
slight  jaundice ;  intermittent  attacks  of  fever ;  urine  dark  ;  no  albumen ; 
thirst  ;  restlessness. 

Treatment. — For  two  days  he  was  treated  with  iron,  but  as  it  made  him 
worse  (before  admission  to  hospital  he  had  taken  large  quantities  of  iron  and 
quinine  without  benefit)  arsenic  was  then  substituted  (maximum  dose  =  12  drops 
daily). 

Immediate  result.— Under  the  arsenic  rapid  and  remarkable  improvement 
took  place.  At  the  end  of  88  days  the  patient  was  discharged  from  hospital 
apparently  quite  well. 

Subsequent  progress  and  Ultimate  result. — Not  known. 

Case  recorded  in  the  "Edinburgh  Medical  Journal,"  November  1877. 


CASE  III. — Male,  aged  34,  grocer's  assistant,  admitted  to  the  Newcastle 
Infirmary  on  10th  June  1875,  suffering  from  all  the  typical  symptoms  of 
pernicious  anaemia. 

Duration. — 2  years. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  ;  great  weakness  and  prostration  ;  some  loss 
of  weight ;  shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles 
greatly  diminished  in  number ;  many  megalocytes  and  microcytes  ;  marked 
poikilocytosis  ;  apparent  nucleation  of  red  corpuscles  ;  white  corpuscles  dimin- 
ished in  number;  area  of  cardiac  dulness  somewhat  increased;  well-marked 
mitral  systolic  murmur  ;  loud  venous  hum  in  the  neck  ;  dilatation  of  external 
jugular  veins;  pulse  100,  very  weak,  irregular;  retinal  haemorrhages;  some 
swelling  of  feet ;  tongue  smooth,  pale,  moist  ;  occasional  vomiting  ;  occasional 
fever  ;  great  restlessness  ;  urine  normal  in  colour. 

Treatment. — Iron  and  quinine,  lime  juice  and  stimulants. 

Result. — No  improvement  ;  death  a  fortnight  after  admission. 

Post-mortem  appearances  typical. 

Case  recorded  in  the  "  Edinburgh  Medical  Journal,"  November  1877. 


CASE  IV. — Male,  aged  28,  foreign  sailor,  was  admitted  to  the  Newcastle 
Infirmary  on  16th  August  1S75,  suffering  from  profound  pernicious 
anaemia. 

Duration. — 7  months. 

Apparent  cause. — Attack  of  yellow  fever  seven  months  previously. 

Symptoms. — Profound  anaemia ;  profound  prostration  ;  loss  of  weight  and 
emaciation  ;  shortness  of  breath  and  palpitation  on  exertion  ;  great  diminution 
of  red  corpuscles  ;  many  megalocytes  and  microcytes  ;  marked  poikilocytosis  ; 
apparent  nucleation  of  the  red  corpuscles  ;  white  corpuscles  diminished  in 
number  ;  soft  systolic  murmur  at  the  base  of  the  heart ;  loud  venous  hum  in  the 
neck;  pulse  84,  small  and  weak;  retinal  haemorrhages;  slight  oedema  of  eyelids  ; 


PERNICIOUS   AN/EMIA.  Ill 

diarrhoea  ;   tongue  smooth,  pale,  moist  ;  constant  thirst  ;    urine  pale,  trace  of 
albumen. 

Treatment. — Quinine,  astringents  and  stimulants  were  administered. 

Result. — No  improvement  ;  death  16  days  after  admission. 

Post-mortem  appearances  characteristic. 

Case  recorded  in  the  "Edinburgh  Medical  Journal,"  November  1877. 


CASE  V. — Female,  aged  29,  married  woman,  seen  in  consultation  14th 
September  1875,  suffering  from  profound  pernicious  anaemia. 

Duration. — 8  months. 

Apparent  cause. — None  ;  the  anaemia  developed  after  the  last  confinement 
(labour  easy,  no  excessive  loss  of  blood). 

Symptoms. — Profound  anaemia  and  prostration  ;  no  loss  of  weight  ;  short- 
ness of  breath  and  palpitation  on  exertion  ;  blood  not  examined  ;  heart  slightly 
increased  in  size  ;  loud  blowing  murmurs  at  the  base  of  the  heart  and  in  the 
vessels  of  the  neck  ;  retinal  haemorrhages  ;  vomiting  ;  diarrhoea  ;  urine  very 
pale,  no  albumen. 

Treatment. — Iron,  astringents  and  stimulants. 

Result. — -No  improvement  ;  the  patient  died  12  days  after  the  consultation. 

Post-mortem  examination  not  allowed. 


CASE  VI. — -Male,  aged  38,  a  chemical  worker,  was  admitted  to  Newcastle 
Infirmary  on  26th  November  1875,  suffering  from  profound  pernicious 
anaemia. 

Duration. — "jh  months. 

Supposed  cause. — Exposure  to  cold,  wet  and  working  in  "  gas." 

Symptoms. — Profound  anaemia  and  prostration  ;  slight  loss  of  weight  ;  short- 
ness of  breath  and  palpitation  on  exertion  ;  great  debility ;  red  corpuscles 
markedly  diminished  in  number  ;  many  megalocytes  and  microcytes  ;  marked 
poikilocytosis  ;  apparent  nucleation  of  red  corpuscles  ;  white  corpuscles  dimin- 
ished in  number  ;  heart  of  normal  size  ;  loud  blowing  systolic  murmurs  at  all 
the  cardiac  orifices,  the  mitral  being  most  marked  ;  pulse  76,  regular,  of  fair 
strength  ;  loud  venous  hum  in  the  neck  ;  external  jugular  veins  distended  and 
prominent  ;  retinal  haemorrhages  ;  some  dropsy  of  feet  and  face  ;  tongue  clean, 
pale  and  moist  ;  occasional  vomiting  ;  frequent  diarrhoea  ;  occasional  fever  ; 
urine  very  pale  ;  numbness  of  hands  and  feet  ;  exaggeration  of  superficial 
reflexes. 

Treatment. — For  the  first  three  weeks  after  admission,  iron,  quinine  and 
phosphorised  cod-liver  oil  were  administered  without  benefit  ;  arsenic  was  then 
given  in  gradually  increasing  doses  (maximum  dose,  48  drops  daily). 

Immediate  result. — Remarkable  and  rapid  improvement  under  the  arsenical 
treatment ;  the  patient  was  discharged  apparently  quite  well  on  20th  January 
I^76,  55  days  after  admission. 

Subsequent  progress. — He  remained  well  for  12  years  ;  then  relapsed  ;  was 
again  admitted  to  Newcastle  Infirmary  under  the  care  of  Professor  Philipson  ; 
arsenic  again  administered  with  temporary  improvement. 

Ultimate  result.— Again  relapsed  and  finally  died  from  the  disease  thirteen 
years  and  nine  months  after  the  first  attack. 

Case  recorded  in  the  "  Edinburgh  Medical  Journal,"  November  1877,  and 
Atlas  of  Clinical  Medicine,"  Vol.  iii.,  p.  142. 


112  DISEASES   OF   THE   BLOOD. 

CASE  VII. — Female,  aged  31,  married  woman,  seen  in  consultation  on  27th 
March  1877,  suffering  from  profound  anaemia,  apparently  pernicious  in 
character. 

Duration. — 5  months. 

Apparent  cause. — None  ;  the  anaemia  developed  during  the  last  pregnancy  ; 
the  confinement  was  easy,  there  was  no  excessive  loss  of  blood. 

Symptoms. — Profound  anaemia  and  prostration  ;  no  loss  of  weight  ;  short- 
ness of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished 
in  number  ;  many  megalocytes  and  microcytes  ;  marked  poikilocytosis  ;  appa- 
rent nucleation  of  red  corpuscles  ;  no  excess  of  white  corpuscles  ;  some  swelling 
of  feet  ;  retinal  haemorrhages  ;  vomiting  ;  diarrhoea. 

Treatment. — Arsenic  was  tried,  but  disagreed  even  in  small  doses  (maximum 
dose  of  arsenic  =  6  drops  daily).  The  patient  ultimately  recovered  under  large 
doses  of  carbonate  of  iron  (a  fact  which  perhaps  throws  some  doubt  upon  the 
diagnosis). 

Subsequent  progress  and  Ultimate  result. — Not  known. 

Case  recorded.— "  Edin.  Med.  Journal,"  Nov.  1877. 


CASE  VIII. — Male,  aged  47,  pitman,  was  admitted  to  Newcastle  Infirmary 
on  6th  September  1877,  suffering  from  all  the  characteristic  symptoms  of 
pernicious  anaemia. 

Duration. — 1  year. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia ;  great  debility  ;  slight  loss  of  weight  ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly 
diminished  in  number  ;  many  megalocytes  and  microcytes  ;  marked  poikilo- 
cytosis ;  apparent  nucleation  of  the  red  corpuscles  ;  no  excess  of  white  cor- 
puscles ;  heart's  action  feeble  ;  pulse  very  weak  ;  retinal  haemorrhages  ;  some 
swelling  of  feet  ;  frequent  diarrhoea  ;  slight  jaundice  ;  thirst. 

Treatment. — The  patient  remained  in  hospital  only  4  days  ;  then  insisted  on 
going  home  ;  no  treatment  adopted. 

Subsequent  progress  and  Ultimate  result.— Not  known. 

Case  recorded  in  the  "Edinburgh  Medical  Journal,"  November  1877. 


CASE  IX. — Male,  aged  17,  errand  boy,  admitted  to  the  Newcastle  Infirmary  on 
2 1st  February  1878,  suffering  from  profound  anaemia  and  vomiting. 

Duration. — 1  year. 

Apparent  cause. — Not  known  ;  the  anaemia  developed  (or  perhaps  was  first 
noticed)  after  an  attack  of  vomiting.  When  10  years  of  age  had  an  attack  of 
inflammation  of  the  bowels. 

Symptoms. — Profound  anaemia  and  prostration  ;  some  loss  of  weight  ;  short- 
ness of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished 
in  number,  many  megalocytes  and  microcytes,  marked  poikilocytosis  ;  apparent 
nucleation  of  the  red  corpuscles  ;  slight  excess  of  whites  ;  loud  venous  hum  in 
the  neck  ;  heart  of  normal  size  ;  soft  mitral  systolic  murmur ;  pulse  very  quick 
(120-130),  and  of  low  tension  ;  no  retinal  haemorrhages  ;  slight  swelling  of  feet  ; 
frequent  vomiting  ;  thirst  ;  dulness,  apparently  due  to  hydrothorax,  over  the 
base  of  each  lung. 


PERNICIOUS   ANEMIA.  113 

Diagnosis  difficult ;  but  as  there  did  not  appear  to  be  any  evidence  of  local 
disease  (in  stomach,  etc.),  and  as  the  microscopical  characters  of  the  blood 
appeared  to  be  characteristic,  I  concluded,  though  with  hesitation,  that  the  case 
was  one  of  pernicious  anaemia.  I  feel  considerable  doubt  as  to  the  correctness 
of  this  view. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose,  27  drops 
daily),  iron,  quinine,  stomachics. 

Immediate  result. — No  improvement.  After  being  in  hospital  for  53  days, 
the  patient  was  seized  with  pain  in  the  abdomen,  vomiting  and  collapse,  and 
died  somewhat  suddenly. 

Post-mortem  examination  not  allowed. 


CASE  X. — Female,  aged  51,  married  woman,  seen  in  consultation  on  31st 
March  1889,  suffering  from  profound  pernicious  anaemia. 

Duration. — Said  to  be  2  or  3  months  ;  short  of  breath  for  2  or  3  years,  but 
not  markedly  anaemic  till  2  months  ago. 

Apparent  cause. — Formerly  very  subject  to  diarrhoea  and  bleeding  piles. 
No  diarrhoea  or  loss  of  blood  for  more  than  a  year ;  haematemesis  a  year  ago. 

Symptoms. — Profound  anaemia  and  prostration  ;  no  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished  in 
number ;  many  megalocytes  and  microcytes  ;  moderate  poikilocytosis  ;  appa- 
rent nucleation  of  red  corpuscles  ;  ?  organisms  ;  heart  somewhat  dilated  ; 
systolic  murmurs  at  base  and  apex  ;  veins  in  the  neck  distended  ;  pulse  markedly 
jerking  in  character  ;  retinal  haemorrhages  ;  occasional  vomiting  ;  no  diarrhoea 
lately  ;  some  swelling  of  feet  ;  marked  leucoderma. 

Treatment. — Arsenic  was  tried  but  only  in  small  doses  as  it  disagreed 
(maximum  dose  =  6  minims  daily)  ;  then  Beta-naphthol  and  thymol. 

Immediate  result. — None  of  these  remedies  produced  any  benefit.  Patient 
died  3  weeks  after  consultation. 

Post-mortem  appearances  typical  of  pernicious  anaemia  ;  some  petechial 
haemorrhages  in  pericardium,  stomach,  and  on  outer  surface  of  intestine  ;  heart 
markedly  fatty  and  dilated  ;  liver  fatty  and  containing  a  large  excess  of  iron  ; 
spleen  slightly  enlarged  and  dark  in  colour  ;  suprarenal  capsules  normal ;  some 
(slight)  old  ulceration  of  the  ilio-caecal  valve. 


CASE  XI. — Male,  aged  54,  Indian  Civil  Servant,  was  seen  in  consultation  on 
14th  September  1886,  suffering  from  profound  anaemia. 

Duration. — 1  year. 

Apparent  cause. — None  ;  ?  gout. 

Symptoms. — Profound  anaemia ;  great  prostration  ;  no  loss  of  weight  ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  moderately 
diminished  in  number  ;  few  megalocytes,  some  microcytes  ;  moderate  poikilo- 
cytosis ;  no  excess  of  whites  ;  heart  slightly  dilated ;  mitral  systolic  murmur  ; 
occasional  angina-like  pains  ;  no  sign  of  aneurism  ;  occasional  vomiting  ;  tongue 
clean,  smooth  and  moist  ;  urine  rather  pale,  no  albumen. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  =  ?). 

Immediate  result. — Improved  considerably  for  a  time  under  arsenic  ;  then 
developed  acute  gout  (from  which  he  had  previously  suffered)  ;  again  improved. 

Subsequent  progress  and  Ultimate  result. — Died  (from  the  disease)  in  the 
South  of  England  about  two  years  after  the  consultation. 

H 


114  DISEASES   OF   THE   BLOOD. 

CASE  XII.— Male,  aged  50,  medical  man,  seen  in  consultation  on  24th  October 
1890,  suffering  from  typical  pernicious  anaemia. 

Duration. — 9  months. 

Apparent  cause.— Several  attacks  of  gastric  influenza,  with  diarrhoea. 

Symptoms. — Profound  anaemia  and  prostration  ;  slight  loss  of  weight  ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly 
diminished  in  number  (1,470,000  per  c.mm.) ;  haemoglobin  =  46  per  cent.; 
many  megalocytes  and  microcytes  ;  marked  poikilocytosis  ;  apparent  nuclea- 
tion  of  red  corpuscles  ;  no  excess  of  white  corpuscles  ;  marked  venous  hum  in 
the  neck  ;  heart  of  normal  size  ;  systolic  pulmonary  murmur  ;  no  retinal  haemor- 
rhages (pupils  very  small) ;  occasional  diarrhoea ;  urine  normal  in  colour ; 
occasional  temporary  trace  of  albumen. 

Treatment. — Small  doses  of  arsenic  (r^th  to  £aih  of  a  grain)  had  been  tried 
but  disagreed,  producing  gastro-intestinal  irritation.  Advised  to  try  gradually 
increasing  doses  of  Fowler's  solution  (maximum  dose  =  ?). 

Immediate  result,  Subsequent  progress  and  Ultimate  result. — Not  known. 

CASE  XIII. — Male,  aged  38,  banker,  seen  in  consultation  9th  September  1890, 
suffering  from  profound  pernicious  anaemia. 

Duration. — 2  years. 

Apparent  cause. — Gastro-intestinal  catarrh  and  diarrhoea,  thought  to  be  due 
to  defective  sanitary  surroundings  (manure  heap  10  feet  from  office  window). 

Symptoms.  —  Profound  anaemia  and  prostration  ;  slight  loss  of  weight ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly 
diminished  in  number  ;  a  few  megalocytes,  some  microcytes  ;  moderate  poikilo- 
cytosis ;  no  increase  of  white  corpuscles  ;  marked  venous  hum  in  the  neck  ;  no 
retinal  haemorrhages  ;  slight  loss  of  blood  from  piles  ;  some  diarrhoea ;  slight 
jaundice  ;  urine  very  dark  ;  an  occasional  trace  of  albumen. 

Treatment. — Arsenic  was  given  in  gradually  increasing  doses  (maximum 
dose  =  60  drops  daily). 

Immediate  result. — Marked  and  rapid  improvement.  On  23rd  February 
1891,  his  doctor  wrote  me  :  "  Mr  B.  is  now  quite  well ;  after  his  visit  to  you  he 
steadily  improved  and  is  now  stout  and  strong." 

Subsequent  progress. — In  March  1891  got  cold,  followed  by  relapse  of  the 
anaemia  ;  the  arsenic  then  discontinued  by  the  advice  of  his  doctor  (from  March 
1891  until  June  1891).  Seen  again  16th  June  1891  ;  profoundly  anaemic  and 
skin  so  deeply  pigmented  that  doctor  suggested  Addison's  disease-  (The 
pigmentation  was  probably  due  to  arsenic  ;  the  patient  had  taken  double  the 
dose  ordered  ;  the  remedy  produced  numbness  in  fingers  and  toes.)  Arsenic 
resumed  ;  again  improved. 

Ultimate  result. —  In  November  1891  again  relapsed.  During  December 
1 89 1  confined  to  bed  with  profound  anaemia  and  gastro-intestinal  catarrh. 
At  beginning  of  January  1892  died  suddenly,  doctor  thought  from  cerebral 
haemorrhage. 

Post-mortem  examination. — None. 


CASE  XIV. — Female,  aged   41,  married   woman,    seen    in    consultation    24th 
March  1891,  suffering  from  profound  anaemia  apparently  pernicious  in 
character. 
Duration. — 18  months. 


PERNICIOUS   ANEMIA.  115 

Apparent  cause. — From  July  to  December  1890  was  extremely  ill  with 
pneumonia  and  recurring  pyrexia  from  which  she  recovered  ;  this  was  followed 
by  profound  anaemia,  paralysis  and  inco-ordination  of  legs. 

Symptoms.— Profound  anaemia  and  prostration;  some  loss  of  weight;  short- 
ness of  breath  and  palpitation  on  exertion ;  blood  not  examined  ;  venous  hum 
in  the  neck ;  systolic  pulmonary  and  mitral  murmurs  ;  retinal  haemorrhages  ; 
repeated  attacks  of  epistaxis  ;  jaundice ;  occasional  fever ;  urine  dark — the 
specimen  which  I  examined  contained  no  albumen. 

Treatment. — Arsenic  was  given  in  gradually  increasing  doses  (maximum  dose 
reached,  42  drops  daily). 

Immediate  result. — The  anaemia  almost  entirely  disappeared  in  the  course 
of  a  few  weeks  ;  the  skin  became  much  bronzed. 

Subsequent  progress. — On  8th  May  a  considerable  quantity  of  pus  was 
suddenly  discharged  in  the  urine  (apparently  due  to  pyelitis).  After  this  the 
patient  suffered  from  recurring  pyrexia,  the  temperature  going  up  to  1050 ;  the 
anaemia  returned ;  epistaxis  recurred,  and  dropsy  developed ;  the  arsenic  had 
to  be  discontinued  ;  quinine,  digitalis  and  stimulants  substituted. 

Ultimate  result.  —The  patient  died  in  July  1891. 

Post-mortem  examination. — The  patient's  doctor  informs  me  that  both 
kidneys  contained  numerous  abscesses  ;  the  other  parts  of  the  body  were  not 
examined. 

Note.— I  had  no  doubt  when  I  saw  this  patient  that  the  case  was  one  of 
pernicious  anaemia ;  it  is  unfortunate,  since  it  was  complicated  with  abscesses  in 
the  kidney,  that  a  complete  post-mortem  examination  was  not  made. 


CASE  XV. — Female,  aged  42,  widow  and  washerwoman,  seen  on  2nd  October 
1892,  suffering  from  profound  anaemia. 

Duration. — 2  years  ;  worse  6  months. 

Apparent  cause. — Loss  of  blood  (pulling  of  tooth  2  years  ago) ;  attack  of 
influenza  and  profound  grief  (loss  of  husband  and  father)  3  months  ago  ;  over- 
work and  insanitary  surroundings. 

Symptoms. — Profound  anaemia  and  debility  ;  no  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion ;  red  corpuscles  markedly  diminished  in 
number  ;  many  megalocytes  and  microcytes ;  marked  poikilocytosis  ;  apparent 
nucleation  of  red  corpuscles  ;  heart  dilated  ;  systolic  pulmonary  and  mitral 
murmurs  ;  venous  hum  in  the  neck  ;  retinal  haemorrhages  ;  swelling  of  feet. 

Treatment. — Large  doses  of  iron  (Robertson's  capsules)  and  increasing 
doses  of  arsenic  (maximum  dose  reached,  30  drops  daily). 

Immediate  result— Rapid  and  remarkable  improvement.  In  two-and-a-half 
months  (15th  December  1892)  the  doctor  wrote  me  saying  "our  patient  is  now  in 
perfect  health,  the  recovery  has  been  remarkable  and  rapid,  and  has  made 
much  talk." 

Subsequent  progress. — The  patient  remained  well  for  nearly  a  year  and  was 
able  to  work  as  a  washerwoman.  Then  (in  March  1893)  had  two  attacks  of 
hepatic  colic,  followed  by  a  return  of  the  anaemia.  Iron  and  arsenic  again 
administered,  but  without  effect.  Seen  on  3rd  May  1894  ;  profoundly  anaemic  ; 
temperature  1040 ;  profoundly  exhausted  and  restless.  Bone-marrow  and 
arsenic  by  rectum  prescribed.     Unable  to  take  medicine. 

Ultimate  result. — Died  two  days  after  my  visit. 

Post-mortem  examination. — None. 


Il6  DISEASES   OF   THE   BLOOD. 

CASE  XVI. — Male,  aged  53,  hotelkeeper,  seen  on  15th  December  1892,  suffering 
from  profound  pernicious  anaemia. 

Duration. — 10  months. 

Apparent  cause. — Chill  while  curling. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight 
(13  stone);  some  shortness  of  breath  on  exertion;  red  corpuscles  markedly 
diminished  in  number ;  some  megalocytes  ;  many  microcytes  ;  marked  poikilo- 
cytosis  ;  apparent  nucleation  of  red  corpuscles  ;  some  excess  of  lymphocytes  ; 
heart  of  normal  size  ;  action  feeble  ;  slight  systolic  murmur  in  aortic  and  mitral 
areas  ;  no  retinal  haemorrhages  ;  some  swelling  of  feet ;  urine  normal  in  colour  ; 
tongue  pale,  smooth  and  moist. 

Treatment. — Arsenic  in  gradually  increasing  doses,  and  Blaud's  pill  capsules, 
prescribed  (maximum  dose  of  arsenic  reached,  18  drops  daily). 

Immediate  result. — Rapid  and  marked  improvement. 

Subsequent  progress. — His  medical  attendant  wrote  me  on  4th  April  1896  : — 
"  He  improved  very  much  after  you  saw  him,  and  was  able  to  go  about  and  do 
his  business  until  December  1894— two  years  afterwards." 

Ultimate  result. — In  the  end  of  December  1894  he  got  a  chill ;  died  from 
congestion  of  the  hmgs  (pneumonia)  in  the  beginning  of  January  1895.  He  took 
the  arsenic  nearly  constantly  ;  indeed,  whenever  he  stopped  it  he  fell  back." 

Post-mortem  examination. — None. 

CASE  XVII. —  Male,  aged  54,  shopkeeper,  seen  in  consultation  in  July  1894, 
suffering  from  profound  anaemia. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  some  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  blood  not  examined  ;  retinal  haemor- 
rhages ;  some  swelling  of  feet  ;  occasional  vomiting  and  diarrhoea  ;  urine  of 
normal  colour. 

Treatment. — Iron  (Robertson's  capsules)  and  arsenic  in  gradually  increasing 
doses  (maximum  dose  reached,  10  drops  daily)  prescribed. 

Immediate  result. — Marked  temporary  improvement. 

Subsequent  progress  and  Ultimate  result. — Relapse  9  months,  and  death 
1 8  months  afterwards. 

Post-mortem  examination. — None. 

CASE  XVIII. — Female,  aged  62,  married  woman,  seen  in  consultation  on  17th 
August  1894,  suffering  from  profound  anaemia. 

Duration. —  1  year. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  some  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  blood  not  examined ;  a  systolic  murmur 
in  all  the  cardiac  areas  ;  heart  somewhat  dilated  ;  venous  hum  in  the  neck  ;  no 
retinal  hemorrhages  ;  some  swelling  of  feet ;  occasional  vomiting  and  diarrhoea  ; 
tongue  pale,  smooth  and  moist  ;  slight  jaundice  ;  urine  of  normal  colour,  and 
contains  some  albumen  (temporary). 

Treatment. — Arsenic  in  gradually  increasing  doses  prescribed  (maximum 
dose  =  ?). 

Immediate  result. — Patient  improved  considerably. 

Subsequent  progress  and  Ultimate  result. — Not  known. 


PERNICIOUS   ANAEMIA.  117 

CASE  XIX. — Male,  aged  63,  banker,  seen  in  consultation  on  16th  December 
1894,  suffering  from  profound  pernicious  anaemia. 

Duration. — 6  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility ;  some  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  red  corpuscles  number  1,125,000  per 
c.mm.  ;  haemoglobin  =  35  per  cent. ;  many  megalocytes  and  microcytes  ;  marked 
poikilocytosis  ;  apparent  nucleation  of  red  corpuscles  ;  no  excess  of  white  cor- 
puscles ;  heart  somewhat  dilated  ;  soft  blowing  murmurs  in  all  the  cardiac 
areas  ;  jugular  veins  markedly  distended  and  pulsating  ;  venous  hum  in  the 
neck  ;  retinal  haemorrhages  ;  slight  swelling  of  feet  ;  occasional  vomiting  and 
diarrhoea  ;  slight  jaundice  ;  irregular  fever  ;  urine  dark  in  colour.     No  albumen. 

Treatment. — Had  been  treated  with  iron  and  tonics  without  any  benefit. 
Arsenic  and  bone-marrow  advised  ;  but  the  day  after  consultation  patient 
became  very  excited,  and  talked  in  a  confused  incoherent  way  ;  he  denounced 
all  sorts  of  drugs  and  poisons,  spoke  rather  boastingly  of  what  he  could  do  for 
himself,  that  he  knew  "  to  a  grain  "  what  amount  of  food  he  should  take,  etc.  At 
times  he  got  quite  ravelled  and  used  wrong  words  to  express  himself.  In  the 
evening  he  was  more  composed  and  rather  disinclined  to  speak.  Next  morning 
doctor  hurriedly  summoned  (at  8  A.M.)  as  he  was  greatly  distressed  by  pal- 
pitation.    When  doctor  arrived  was  unconscious. 

Result. — Patient  died  shortly  afterwards — 2  days  after  the  consultation. 

Post-mortem  examination. — None. 


CASE  XX. — Male,  aged  53,  carter,  seen  as  an  out-patient  at  the  Edinburgh 
Royal  Infirmary  on  21st  February  1893,  suffering  from  profound  per- 
nicious anaemia. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  some  loss  of  weight ;  marked 
shortness  of  breath  and  palpitation  on  exertion ;  red  corpuscles  markedly 
diminished  in  number  ;  some  megalocytes  ;  many  microcytes  ;  marked  poikilo- 
cytosis ;  apparent  nucleation  of  red  corpuscles  ;  no  excess  of  white  corpuscles  ; 
heart's  action  feeble  ;  no  murmur  ;  retinae  not  well  seen;  some  swelling  of  feet  ; 
urine  dark  in  colour  ;  trace  of  albumen. 

Treatment. — Iron,  and  arsenic  in  gradually  increasing  doses  prescribed 
(maximum  dose  reached,  20  drops  daily). 

Immediate  result. — Between  February  and  June  he  improved  very  much,  the 
oedema  of  the  legs  disappeared  and  he  was  able  to  get  about. 

Subsequent  progress. — In  June  1893  the  anaemia  returned  and  the  patient 
consulted  another  medical  man,  who  diagnosed  kidney  disease.  The  arsenic 
was  discontinued. 

Ultimate  result. — After  this  the  patient  got  rapidly  worse  and  died  30th  July 
1893.  The  medical  man  who  sent  him  to  me  wrote  me  on  2nd  April  1898, 
saying  :  "  His  widow  tells  me  to-day  that  all  the  time  he  was  under  your  treat- 
ment he  did  well,  and  when  he  gave  it  up  he  got  rapidly  worse.  Indeed,  there 
was  a  scene  between  her  and  Dr  A.,  during  which  she  forgot  herself  and  told 
Dr  A.  that  her  husband  had  been  killed." 

Post-mortem  examination. — None. 


Il8  DISEASES   OF  THE   BLOOD. 

CASE  XXI.— Male,  aged  51,  publisher,  seen  in  consultation  on  6th  February 
1895,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  some  loss  of  weight;  shortness 
of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished  in 
number  (lowest  count  900,000)  ;  haemoglobin  not  estimated  ;  marked  poikilo- 
cytosis  ;  loud  venous  hum  in  neck  ;  heart  somewhat  dilated  ;  systolic  murmurs 
at  base  and  apex  ;  during  relapse,  distension  and  pulsation  of  jugular  veins ; 
retinal  haemorrhages  ;  slight  jaundice  ;  occasional  vomiting ;  no  diarrhoea  ; 
tongue  pale,  smooth  and  moist  ;  urine  normal  in  colour. 

Treatment. — Arsenic  was  prescribed  (maximum  dose  reached,  12  minims 
daily). 

Immediate  result. —  Marked  improvement  took  place  and  the  patient  was 
able  for  a  time  to  resume  his  business. 

Subsequent  progress. — In  January  1896,  the  anaemia  relapsed  ;  another 
consultant  was  called  in  and  diagnosed  the  condition  as  dyspepsia  ;  patient  was 
treated  accordingly,  the  arsenic  being  discontinued.  No  improvement  took 
place.  Seen  again  2nd  June  1896,  in  the  last  stage  of  pernicious  anaemia. 
Arsenic  and  bone-marrow  prescribed.  Could  not  take  the  arsenic.  On  8th 
June  1896,  very  much  worse.     Transfused  with  blood  on  9th  June  1896. 

Ultimate  result. — Died  10th  June  1896. 

Post-mortem  examination. — None. 


CASE  XXII. — Male,  aged  66,  stockbroker,  seen  in  consultation  on  28th 
September  1895,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — Dyspepsia  and  diarrhoea  (doubtful  if  diarrhoea  the  cause 
or  consequence). 

Symptoms. — Profound  anaemia  and  debility  ;  slight  loss  of  weight  ;  short- 
ness of  breath  and  palpitation  on  exertion  ;  blood  not  examined  ;  retinal 
haemorrhages ;  swelling  of  feet ;  occasional  vomiting  and  diarrhoea  ;  occasional 
fever  ;  urine  normal  in  colour. 

Treatment. — Arsenic  in  gradually  increasing  doses  prescribed  ;  was  only 
able  to  take  the  arsenic  in  small  doses  (3  drops,  subsequently  reduced  to  1  drop 
— maximum  dose  reached,  9  drops  daily,  but  only  for  a  few  doses).  Bone- 
marrow  was  also  tried,  but  did  no  good. 

Subsequent  progress  and  Ultimate  result. — There  was  no  improvement  ;  the 
patient  died  3  weeks  after  the  consultation. 

Post-mortem  examination. — None. 


CASE  XXIII. — Male,  aged  57,  engineer,  seen  in  consultation  on  8th  April  1896, 
suffering  from  profound  anaemia  and  diarrhoea. 

Duration. — 18  months. 

Apparent  cause. — None.  Dyspeptic  for  12  or  15  years.  For  18  months 
excessive  appetite  and  recurring  attacks  of  diarrhoea,  with  heat  and  excoriation 
of  anus  (increased  by  butcher  meat  and  stimulants). 

Symptoms.— Profound  anaemia  and  debility;  slight  loss  of  weight;  shortness 


PERNICIOUS   ANAEMIA.  119 

of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished  in 
number;  some  megalocytes  ;  many  microcytes;  moderate  poikilocytosis;  apparent 
nucleation  of  red  corpuscles  ;  no  excess  of  white  corpuscles  ;  retinal  haemor- 
rhages ;  frequent  diarrhoea ;  tongue  pale,  smooth  and  moist;  no  febrile  attacks  ; 
urine  of  normal  colour. 

Treatment. — A  milk  diet,  salicylate  of  bismuth  for  diarrhoea,  iron  and 
arsenic.  The  iron  disagreed  ;  it  brought  on  diarrhoea.  Was  only  able  to  take 
very  small  doses  of  arsenic,  2  minims  three  times  a  day  (maximum  dose 
reached,  6  minims  daily). 

Immediate  result. — No  improvement. 

Subsequent  progress. — Seen  again  10th  June  1896.  Very  much  worse  in 
every  way  ;  profoundly  anaemic  ;  temperature  ioo°  ;  tongue  dry;  delirious. 

Ultimate  result. — Died  on  12th  June  1896. 

Post-mortem  examination. — None. 


CASE  XXIV. — Male,  aged  49,  formerly  a  shunter  now  a  cart-weigher,  seen  as 
an  out-patient  at  the  Edinburgh  Royal  Infirmary  on  3rd  December  1896, 
suffering  from  profound  pernicious  anaemia. 

Duration. —  1  year. 

Apparent  cause. — In  October  1893,  run  over  by  an  engine  ;  right  arm  and 
leg  amputated ;  never  so  well  since,  but  able  to  work  till  lately. 

Symptoms. — Profound  anaemia  and  debility  ;  no  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly  diminished  in 
number ;  few  megalocytes  ;  many  microcytes  ;  marked  poikilocytosis  ;  apparent 
nucleation  of  red  corpuscles  ;  no  excess  of  white  corpuscles  ;  venous  hum  in 
neck  ;  heart  somewhat  dilated  ;  systolic  murmur  in  pulmonary  area  ;  no  retinal 
haemorrhages  ;  occasional  vomiting;  slight  jaundice  ;  urine  dark  in  colour. 

Treatment. — Gradually  increasing  doses  of  arsenic  (maximum  dose  reached, 
36  drops  daily). 

Immediate  result. — Made  rapid  and  continuous  improvement. 

Subsequent  progress. — Able  to  return  to  work  on  15th  February;  worked 
(as  a  cart- weigher)  till  13th  August ;  was  then  laid  up  with  slight  return  of  the 
anaemia ;  off  work  six  weeks  ;  again  cured  by  arsenic.  Worked  till  9th  of 
January  1898,  when  had  again  to  leave  off  because  of  the  anaemia  ;  has  not 
worked  since  ;  lost  his  wife  at  the  beginning  of  February  1898  and  has  been 
much  worse  since.  Is  taking  30  drops  of  arsenic  daily  ;  for  a  time  tried  bone- 
marrow,  but  could  not  take  it  as  it  made  him  sick. 

Profoundly  anaemic  and  debilitated  ;  no  retinal  haemorrhages  ;  urine  dark 
in  colour  ;  no  albumen  ;  depositing  large  quantities  of  uric  acid  ;  red  corpuscles 
markedly  diminished  in  number  ;  moderate  poikilocytosis  ;  some  megalocytes  ; 
many  microcytes  ;  apparent  nucleation  of  the  red  corpuscles  ;  white  corpuscles 
not  increased  ;  skin  very  dark  (arsenic). 

The  dose  of  arsenic  was  increased  to  36  drops  daily,  but  the  patient  did  not 
improve. 

Admitted  to  the  Edinburgh  Royal  Infirmary  on  3rd  May  1898  in  a  state  of 
extreme  anaemia  and  exhaustion  ;  some  oedema  of  feet  and  face  ;  no  albumen. 
On  the  17th  and  20th  May  there  was  some  epistaxis. 

Ultimate  result. — Died  on  20th  May. 

Post-mortem  examination. — Not  allowed. 


120 


DISEASES   OF   THE   BLOOD. 


The  following   table   shows   the   condition   of  the   blood  during  the  final 
illness  : — 


Date. 

Red 

Corpuscles. 

Haemoglobin. 

Colour 

Index 

(Corrected). 

White 
Corpuscles. 

4th  April 

1898 

1,450,000 

46  per  cent. 

1-7 

3,220 

nth      „ 

>> 

1,000,000 

28         „ 

i-5 

4,000 

1 8th      „ 

5) 

1,075,000 

38 

2. 

25th      „ 

>) 

1,050,000 

40 

2. 

3,500 

6th  May 

>> 

916,700 

28         „ 

1.6 

2,500 

1 2th      „ 

1) 

867,000 

3°                 » 

i-9 

1,870 

:   18th      „ 

5, 

650,000 

20 

1.6 

4,375 

CASE  XXV.— Female,  aged  54,  married  woman,  admitted  to  Edinburgh 
Royal  Infirmary  on  30th  September  1896,  suffering  from  profound  per- 
nicious anaemia. 

Duration. — 10  months. 

Apparent  cause. — None.  For  20  years  has  had  large  ulcers  on  both  legs. 
Before  admission,  treated  with  iron,  arsenic  (9  drops  daily)  and  bone-marrow, 
without  improvement. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight  ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  995,000  ;  haemo- 
globin  =  28  per  cent.;  colour  index  1.4;  few  megalocytes  ;  many  microcytes  ; 
moderate  poikilocytosis ;  apparent  nucleation  of  red  corpuscles  ;  heart's  action 
very  feeble  ;  heart  somewhat  dilated  ;  systolic  murmurs  in  pulmonary  and  other 
areas  ;  pulse  80,  of  fair  volume,  weak  ;  no  retinal  haemorrhages  ;  occasional 
vomiting  and  diarrhoea;  tongue  clean,  smooth  and  moist;  occasional  slight 
fever  ;  urine  dark  ;  tenderness  of  sternum  and  tibiae. 

Treatment. — Arsenic  in  increasing  doses  prescribed  (maximum  dose  reached, 
42/lrops  daily). 

Immediate  result. — Marked  improvement  so  far  as  appearance  and  symptoms 
were  concerned,  but  no  improvement  in  blood  condition.  On  2nd  November, 
red  corpuscles  1,100,000  ;  haemoglobin  =  33  per  cent.  Patient  was  discharged 
on  2nd  November  1896. 

Subsequent  progress  and  Ultimate  result. — After  leaving  hospital  the  patient 
gradually  got  worse  and  died  on  2nd  February  1897.  In  writing  to  tell  me  of  her 
death,  the  doctor  stated  "she  was  much  improved  by  her  treatment  in  hospital." 

Post-mortem  examination. — None. 


CASE  XXVI. — Male,  aged  53,  gamekeeper,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  3rd  May  1897,  suffering  from  profound  pernicious  anaemia 
and  marked  jaundice. 
Duration. — Probably  2  (at  most  3)  months. 
Apparent  cause. — None. 


PERNICIOUS   ANEMIA. 


121 


Symptoms. — Profound  anaemia  and  debility ;  slight  loss  of  weight ;  marked 
jaundice;  shortness  of  breath  and  palpitation  on  exertion ;  red  corpuscles  num- 
bered 810,000  ;  haemoglobin  =  20  per  cent.  ;  many  megalocytes  and  microcytes  ; 
marked  poikilocytosis ;  apparent  nucleation,  but  no  true  nucleation  of  red  cor- 
puscles;  a  few  Eichhorst's  corpuscles;  white  corpuscles  not  increased;  blood- 
plates  about  normal;  no  organisms  in  blood  ;  heart's  action  feeble ;  no  murmurs ; 
pulse  96,  small,  weak ;  some  swelling  of  feet ;  retinal  haemorrhages  ;  occasional 
vomiting;  constipation;  stools  bright  orange  colour;  no  parasites  in  stools; 
tongue  thickly  furred ;  occasional  fever  ;  urine  very  dark  and  containing  (tem- 
porarily) albumen  and  casts,  and  on  several  occasions  deposited  large  quantities 
of  uric  acid  crystals. 

Treatment. — Was  treated  with  gradually  increasing  doses  of  arsenic 
(maximum  dose  reached,  60  drops  daily). 

Immediate  result. — Remarkable  and  rapid  improvement  took  place.  On 
patient's  admission  (3rd  May  1897)  the  red  corpuscles  numbered  810,000  ; 
haemoglobin  =  20  percent.  At  the  date  of  the  patient's  discharge  (14th  June 
1897)  the  red  corpuscles  numbered  3,420,000  and  the  haemoglobin  =  64  per  cent. 
On  20th  July  1897,  the  red  corpuscles  numbered  4,010,000  ;  haemoglobin  = 
88  per  cent. 

Subsequent  progress.— -The  patient  made  steady  progress  after  leaving  the 
Infirmary.  He  continued  to  take  the  arsenic  regularly  until  the  end  of  October 
1897,  when  by  the  advice  of  his  local  medical  man  he  almost  entirely  gave  it  up. 

In  March  1898,  he  caught  a  slight  chill ;  this  was  followed  by  a  slight  relapse 
of  the  anaemia.    Advised  to  at  once  begin  the  arsenic  again  and  take  it  regularly. 

On  4th  May  1898,  was  examined  at  the  Edinburgh  Royal  Infirmary.  Says 
that  he  has  almost  completely  recovered  from  the  recent  relapse  ;  weight 
12  stone  ;  does  not  look  anaemic  ;  conjunctiva  slightly  bile-stained  ;  urine  dark 
and  contains  a  distinct  quantity  of  albumen  and  excess  of  indican  ;  red  cor- 
puscles number  2,360,000  ;  haemoglobin  =  60  per  cent.;  a  few  megalocytes  and 
microcytes  ;  slight  poikilocytosis ;  white  corpuscles  diminished  in  number 
(3,440  per  c.mm.)  ;  is  taking  36  drops  of  Fowler's  solution  daily. 

The  condition  of  the  blood  at  different  dates  is  shown  in  the  following  table  : — 


Date. 

Number  of  Red 
Corpuscles. 

Haemoglobin. 

Colour  Index 
(Corrected). 

Whites. 

5th  May 

1 897 

8l0,000 

20  per  cent. 

i-3 

10th     „ 

5, 

970,000 

28 

i.6 

1 3,000* 

18th     „ 

,, 

1,710,000 

40        „ 

1.2 

12,000* 

23rd     „ 

5, 

2,650,000 

42 

.8 

8th  June 

11 

2,700,000 

64 

i-3 

14th     „ 

11 

3,420,000 

64 

1. 

12,000* 

20th  July 

11 

4,010,000 

88 

1.2 

14,000* 

4th  May 

I898 

2,360,000 

60 

1.4 

3,440 

13th     „ 

11 

2,958,340 

7o        „ 

i-3 

3,439 

Case  recorded  in  the  "  Lancet  "  of  24th  July  1897,  p.  197. 


*  These  counts  were  probably  erroneous. 


122 


DISEASES   OF   THE   BLOOD. 


CASE  XXVII. — Female,  aged  52,  single,  children's  nurse,  was  admitted  to  the 
Edinburgh  Royal  Infirmary  on  17th  May  1897,  suffering  from  profound 
anaemia,  weakness  and  pigmentation  of  the  skin. 

Duration. — 2  years. 

Apparent  cause. — None.  The  disease  commenced  with  weakness  and  loss 
of  flesh  and  ansemia  ;  these  symptoms  were  followed  by  pigmentation  of  the 
skin,  epistaxis  and  jaundice.  Six  months  ago  Dr  Garnet  of  Massachusetts 
Hospital  diagnosed  the  case  as  Addison's  disease. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight  ; 
shortness  of  breath  on  exertion  ;  considerable  diffused  pigmentation  of  the  skin, 
no  pigmentation  of  nipples,  no  pigmentation  of  buccal  mucous  membrane  ;  red 
corpuscles  numbered  1,400,000,  and  the  haemoglobin  =  25  per  cent;  many 
megalocytes  and  microcytes ;  moderate  poikilocytosis ;  apparent,  but  no  true, 
nucleation  of  red  corpuscles  ;  some  excess  of  lymphocytes  ;  heart's  action 
feeble ;  no  murmurs ;  venous  hum  in  neck ;  pulse  90,  small,  weak ;  no  retinal 
haemorrhages  ;  severe  epistaxis  and  jaundice  some  months  before  admission  ; 
urine  dark  in  colour. 

Diagnosis. — The  case  seemed  to  me  to  be  pernicious  anaemia,  perhaps  com- 
plicated with  Addison's  disease. 

Treatment. — Arsenic  was  given  in  gradually  increasing  doses  (maximum 
dose  reached,  57  minims  per  diem). 

Immediate  result. — The  patient  improved  considerably  both  in  appearance  and 
as  regards  her  symptoms,  but  the  blood  condition  remained  much  in  statu  quo. 
She  was  discharged  on  26th  June  1897.  Shortly  before  this  date  the  red  cor- 
puscles numbered  1,310,000  and  the  haemoglobin  equalled  44  per  cent.  She  had 
gained  5^  lbs.  in  weight. 

The  following'  table  shows  the  condition  of  the  blood  at  different  dates  : — 


Date. 

Red  Corpuscles.       Haemoglobin, 

r                      per  cent. 

Colour  Index         whites 
(Corrected). 

1 8th  May  1897 

1,400,000 
I,Il8,000 

1,131,000 

25 

33 

44 

.8 
i-5 
1-9 

1 

Subsequent  progress  and  Ultimate  result. — Not  known. 


CASE  XXVIII. — Male,  aged  36,  reporter,  seen  on  30th  June  1897,  suffering 
from  profound  and  causeless  anaemia,  apparently  pernicious. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  shortness  of  breath  on  exertion ; 
red  corpuscles  markedly  diminished  in  number  ;  few  megalocytes  ;  many  micro- 
cytes ;  a  few  Eichhorst's  corpuscles  ;  moderate  poikilocytosis  ;  lymphocytes  in 
excess  ;  venous  hum  in  neck  ;  systolic  murmurs  in  all  the  areas,  loudest  in  pul- 
monary and  tricuspid  ;  slight  jaundice  ;  no  retinal  haemorrhages  ;  occasional 
vomiting  and  diarrhoea  ;  urine  dark  ;  no  albumen. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  reached, 


PERNICIOUS   ANEMIA.  1 23 

60  drops  of  Fowler's  solution  daily)  ;  and  salicylate  of  bismuth  for  the  diarrhoea, 
which  was  a  prominent  symptom. 

Immediate  result. — Rapid  and  continuous  improvement. 

Subsequent  progress.— On  12th  April  1898,  his  medical  man  wrote  me  : 
"  Patient  is  perfectly  well.  I  pushed  up  the  arsenic  until  he  took  one  drachm  of 
the  liquor  daily." 

Ultimate  result. — Cure  {Iftro  tern.). 


CASE  XXIX. — Female,  aged  49,  single,  no  occupation,  seen  in  consultation 
on  20th  July  1897,  suffering  from  advanced  pernicious  anaemia. 

Duration. — 1  year. 

Apparent  cause. — None.  Had  for  a  time  improved  under  iron  and  arsenic  ; 
then  relapsed  ;  only  able  to  take  the  arsenic  in  very  small  doses  (two  or  three 
minims)  as  it  caused  irritation  of  the  stomach. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight  ; 
shortness  of  breath  and  palpitation  on  exertion  ;  red  corpuscles  markedly 
diminished  in  number  ;  many  megalocytes  and  microcytes  ;  marked  poikilo- 
cytosis ;  blowing  murmurs  in  all  the  cardiac  areas ;  venous  hum  in  neck,  also 
over  occiput ;  retinal  haemorrhages  ;  occasional  vomiting  and  diarrhaea  ;  some 
swelling  of  feet  ;  urine  normal  in  colour  ;  no  albumen. 

Treatment. — Advised  to  make  another  attempt  to  take  the  arsenic  in  larger 
doses  ;  salicylate  of  bismuth  also  prescribed  for  the  diarrhoea,  which  was  very 
troublesome.  The  patient's  medical  man  informs  me  that  "  she  could  never 
take  more  than  3  drops  of  arsenic  (maximum  dose  reached,  9  minims  daily), 
and  that  only  for  a  few  days  at  a  time." 

Result. — There  was  no  improvement  ;  the  patient  died  on  21st  November 
1897. 

Post-mortem  examination. — The  doctor  informs  me  that  "  the  post-mortem 
appearances  were  highly  characteristic  of  pernicious  anaemia ;  portions  of  the 
organs  were  sent  to  one  of  the  laboratories  in  Edinburgh,  but  have  been 
mislaid." 


CASE  XXX. — Female,  aged  40,  single,  no  occupation,  seen  in  consultation 
on  25th  September  1897,  suffering  from  advanced  pernicious  anaemia. 

Duration. — 9  months. 

Apparent  cause. — None.  Ten  years  previously  the  patient  had  been  pro- 
foundly anaemic  but  had  recovered.  The  patient  had  been  treated  with  arsenic, 
but  had  not  been  able  to  take  it  except  in  small  doses  (maximum  dose  reached, 
9  drops  daily,  and  this  only  for  a  short  time). 

Symptoms. — Profound  anaemia  and  debility ;  some  loss  of  weight ;  shortness 
of  breath  and  palpitation  on  exertion  ;  the  blood  was  not  examined ;  heart 
dilated ;  systolic  murmurs  in  pulmonary,  mitral  and  tricuspid  areas ;  pulsation 
in  veins  of  neck ;  loud  venous  hum  ;  retinal  haemorrhages ;  diarrhoea ;  urine 
normal  in  colour ;  no  albumen. 

Treatment. — Advised  to  make  a  fresh  attempt  to  take  the  arsenic  in  gradually 
increasing  doses.     Was  unable  to  do  so,  as  it  produced  vomiting. 

Result. — There  was  no  improvement ;  the  patient  gradually  became  weaker, 
without  any  fresh  developments,  and  died  eleven  days  after  the  consultation. 

Post-mortem  examination. — None. 


124  DISEASES   OF   THE   BLOOD. 

CASE  XXXI. — Female,  aged  16,  child's  nurse,  was  admitted  to  Edinburgh 
Royal  Infirmary  on  19th  September  1890,  suffering  from  profound 
anaemia,  apparently  pernicious. 

Duration. — 3  years. 

Apparent  cause. — Vomiting  of  blood,  the  result  apparently  of  ulceration  of 
the  stomach  3  years  previously  ;  quite  well  before  this  ;  never  well  since  ;  has 
vomited  frequently  and  become  paler  and  weaker.  On  3  or  4  occasions  (since 
the  first  attack)  has  vomited  blood  or  "coffee-grounds";  has  several  times  im- 
proved and  several  times  relapsed ;  got  better  before  under  Blaud's  pills  ;  the 
condition  seems  therefore  to  have  been  chlorosis  and  ulceration  of  the  stomach  ; 
worse  since  an  attack  of  influenza  in  January  1890.  No  pain  in  stomach. 
Some  constipation. 

Symptoms.  —  Profoundly  anaemic  and  debilitated;  some  loss  of  weight; 
shortness  of  breath  and  palpitation  on  exertion  ;  menstruation  regular  every 
three  weeks  and  too  profuse  till  last  period  which  she  missed;  red  corpuscles  = 
900,000;  haemoglobin  =  15  per  cent.;  on  microscopical  examination  the  blood 
changes  were  much  less  marked  than  I  had  expected,  considering  the  extreme 
diminution  of  the  red  corpuscles  ;  there  were  some  megalocytes,  some  micro- 
cytes  and  a  moderate  degree  of  poikilocytosis  ;  loud  venous  hum  in  neck  ; 
systolic  murmur  in  pulmonary  and  mitral  areas  ;  retinal  haemorrhages  ;  some 
swelling  of  feet  ;  urine  dark  in  colour ;  no  albumen  ;  skin  in  places  deeply 
pigmented  as  if  from  Addison's  disease  ;  areolae  of  nipples  dark  brown  ;  several 
dark  bands  round  waist  where  clothes  tied ;  no  pigmentation  of  mucous 
membranes. 

Diagnosis.  —  Difficult  ;  the  case  seemed  without  doubt  to  be  originally 
chlorosis  and  ulceration  of  the  stomach  ;  when  admitted  to  hospital  the  great 
diminution  of  the  red  corpuscles,  the  retinal  haemorrhages  and  the  progressive 
course  of  the  anaemia  notwithstanding  the  administration  of  large  doses  of  iron 
were  suggestive  of  pernicious  anaemia ;  the  pigmentation  of  the  skin  was 
suggestive  of  Addison's  disease.  After  carefully  watching  the  case,  I  came  to 
the  conclusion  that  the  case  was  probably  a  combination  of  pernicious  anaemia 
and  Addison's  disease  following  chlorosis  and  ulceration  of  the  stomach. 

Treatment. — Iron  and  arsenic  in  increasing  doses  were  administered 
(maximum  dose  of  arsenic  reached,  12  drops). 

Result. — No  improvement  ;  progressive  diminution  of  the  red  corpuscles 
and  of  the  haemoglobin  without  any  obvious  cause.  The  arsenic  was  badly 
borne.  On  8th  October,  the  patient  complained  of  pain  in  the  stomach  and 
vomited;  pulse  130;  M.T.  99°.6,  E.T.  1020 ;  arsenic  and  iron  discontinued; 
peptonised  milk  and  rectal  feeding.  10th  October  : — Vomiting  less;  pulse  140  ; 
respirations  60  ;  M.T.  99°.6,  E.T.  1010 ;  patient  very  prostrate  ;  commencing 
pneumonia  at  the  base  of  right  lung.  On  12th  October,  pneumonia  of  the  right 
lung  more  advanced;  the  temperature,  which  in  the  morning  was  ioo°.2,  at 
12  a.m.  began  to  rise  rapidly;  at  10  P.M.  it  reached  io5°.4  ;  the  patient  died 
at  11  P.M. 


PERNICIOUS   ANEMIA.  125 

The  following:  table  shows  the  condition  of  the  blood  at  different  dates  : — 


Date. 

Number  of  Red 
Corpuscles. 

Haemoglobin. 

Colour  Index 
(Corrected). 

2 1  st  Sept. 

1890 

900,000 

1 5  per  cent. 

.8 

28th      „ 

5! 

600,000 

10 

.85 

3rd  Oct. 

55 

650,000 

10    .     5, 

78 

6th    „ 

55 

450,000 

3         „ 

.88 

9th     „ 

55 

550,000 

8        „ 

•73 

nth     „ 

55 

450,000 

5 

•55 

Post-mortem  examination. — Not  allowed. 


CASE  XXXII. — Male,  aged  41,  a  farmer,  seen  in  consultation  on  2nd  April 
1894,  suffering  from  profound  pernicious  anaemia. 

Duration. — Six  months. 

Apparent  cause. — None.  Has  for  some  time  been  taking  iron  and  arsenic  in 
small  doses. 

Symptoms. — Profound  anaemia  and  debility  ;  slight  loss  of  weight  ;  shortness 
of  breath  ;  palpitation  ;  red  corpuscles  markedly  diminished  in  number ;  few 
megalocytes  ;  many  microcytes  ;  moderate  poikilocytosis  ;  apparent  nucleation 
of  red  corpuscles  ;  white  corpuscles  not  in  excess  ;  venous  hum  in  neck  ;  retinal 
haemorrhages  ;  tongue  pale,  smooth  and  moist  ;  urine  normal  in  colour ;  no 
albumen. 

Treatment. — Iron  (Robertson's  capsules)  and  arsenic  in  increasing  doses 
(maximum  dose  reached,  24  drops  daily). 

Immediate  result. — On  24th  June  1895,  his  doctor  wrote  me: — Vomited 
blood  (coffee-grounds)  a  few  days  after  consultation.  Took  three  Robertson's 
capsules  three  times  daily  and  arsenic  until  he  reached  24  drops  daily.  He 
rapidly  improved,  in  the  course  of  a  short  time  got  perfectly  well,  and  was  able 
to  do  his  ordinary  (farm)  work.  The  patient's  own  statement  was  :  "  After  the 
consultation  I  went  away  with  a  bound  ;  within  a  week  after  commencing  the 
arsenic  was  better." 

Subsequent  progress. — In  February  i8gj  (n  months  afterwards)  had  a 
relapse  during  the  intense  cold ;  again  soon  got  well  under  the  same  treatment. 

In  July  iSgs(6  months  afterwards)  had  a  second  relapse  ;  stomach  symptoms 
developed  and  the  arsenic  had  to  be  stopped.  As  he  was  not  improving  he 
came  to  Edinburgh  to  see  me. 

He  was  then  (on  23rd  October  18Q5)  profoundly  anaemic,  but  not  much 
thinner;  appetite  fair ;  no  diarrhoea;  no  retinal  haemorrhages;  red  corpuscles 
greatly  reduced;  many  megalocytes  and  microcytes  ;  very  marked  poikilocytosis  ; 
white  corpuscles  not  increased.  Was  advised  to  remain  at  absolute  rest  in  bed 
and  to  continue  the  iron  and  arsenic,  increasing  the  dose  of  arsenic  if  he  can 
manage  it. 


126  DISEASES   OF   THE   BLOOD. 

The  subsequent  progress  of  the  case  is  fully  detailed  in  the  following  state- 
ment which  the  patient's  doctor  has  kindly  sent  me  : — "When  you  saw  Mr  H. 
in  October  1895,  you  advised  rest  with  Blaud's  pills  and  arsenic.  He  came 
home  and  went  to  bed,  and,  with  the  exception  of  getting  up  to  have  his  bed 
made,  remained  in  bed  until  the  middle  of  January  1896.  During  that  time,  he 
was  taking  five  and  six  minims  of  liquor  arsenicalis  with  two  and  sometimes 
three  No.  3  Blaud's  capsules  three  times  daily.  His  appetite  was  good — better 
than  when  he  was  going  about,  he  was  able  to  take  considerable  quantities  of 
nourishment,  nothing  seemed  to  disagree  with  him  ;  he  was  cheerful  and  in 
good  spirits  ;  his  colour  improved  a  good  deal.  About  the  middle  of  January 
1896,  he  began  to  get  out  of  bed  for  a  short  time  daily,  gradually  extending 
the  time  as  he  gained  in  strength.  As  the  season  advanced,  he  began  to  get 
out  of  doors,  and  in  the  month  of  March  did  a  little  light  work.  As  he  felt 
none  the  worse  of  this,  he  gradually  increased  the  amount,  until  by  the  middle 
of  April  1896  he  was  doing  something  nearly  all  day.  From  January  1896  to 
April  1896  I  did  not  see  him  much,  but  I  suppose  he  was  going  on  with  the 
arsenic  and  iron,  though  I  believe  not  with  the  same  regularity  as  before. 

About  the  middle  of  April  i8g6,  I  was  sent  for  and  found  him  in  a  semi- 
collapsed  condition,  pallid,  breathless  and  the  other  anaemic  symptoms  returned. 
On  enquiry  I  found  that  on  the  previous  day  he  had  done  a  full  day's  garden 
work  at  what  is  known  in  this  district  as  'putting  in'  the  garden.  Rest, 
arsenic  and  iron  capsules  were  again  resorted  to.  For  a  time  he  seemed  as  if 
he  would  improve,  but  he  did  not  respond  to  the  treatment  in  the  same  way  as 
before.  Towards  the  end  of  May  1896,  his  appetite  began  to  fail  and  he  had 
occasional  attacks  of  vomiting  (food  and  mucus).  I  diminished  the  dose  of 
arsenic  and  the  stomach  improved  a  little — I  had  got  him  up  to  six  minims 
three  times  daily  but  could  not  get  beyond  that,  as  on  every  attempt  to  do 
so  the  stomach  rebelled.  About  the  end  of  July  1896,  he  had  an  attack  of 
haematemesis.  After  this  date,  he  had  three  attacks  of  vomiting  of  the  same 
nature.  No  growth  or  hardness  could  be  felt  in  the  region  of  the  stomach, 
and  as  he  was  pretty  much  emaciated  I  think  this  could  have  been  made  out 
had  it  existed." 

Ultimate  result. — Patient  died  from  the  disease  on  nth  August  1896. 

Post-mortem  examination. — None. 

CASE  XXXIII.— Male,  aged  54,  clergyman,  seen  in  consultation  on  23rd 
January  1895,  suffering  from  marked  pernicious  anaemia. 

Duration. — Four  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  marked  shortness  of  breath 
on  exertion  ;  palpitation  ;  frequent  fainting  and  giddiness  ;  heart's  action  very 
feeble  and  irregular  ;  heart  somewhat  dilated;  systolic  murmurs  in  pulmonary 
and  mitral  areas ;  venous  hum  in  neck ;  blood  not  examined  ;  no  retinal 
haemorrhages  ;  frequent  and  troublesome  diarrhoea  ;  tongue  pale,  smooth  and 
moist;  urine  of  normal  colour  ;  no  albumen. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  reached, 
40  drops). 

Immediate  result. — Marked  improvement ;  in  the  course  of  a  few  months  the 
patient  appeared  to  be  quite  well. 

Subsequent  progress. — A  year  afterwards,  a  relapse;  the  red  corpuscles  fell 
to  1,000,000 ;  arsenical  treatment  with  bone-marrow  and  iron  again  followed  by 


PERNICIOUS   ANAEMIA.  1 27 

marked  improvement  (maximum  dose  of  arsenic  reached,  40  drops  daily)  ; 
the  red  corpuscles  went  up  to  4,600,000. 

After  some  months,  another  relapse,  the  red  corpuscles  falling  to  1,200,000  ; 
the  patient  became  very  depressed  mentally  and  complained  of  numbness  in 
the  fingers  and  toes.  Seen  again  in  consultation  on  23rd  October  1896  ;  the 
red  corpuscles  now  numbered  3,000,000  ;  there  was  considerable  poikilocytosis. 
Advised  to  continue  the  arsenic,  if  possible  in  larger  doses. 

Ultimate  result. — After  several  ups  and  downs  the  anaemia  again  became 
profound  and  the  patient  ultimately  died  from  the  disease  on   nth  February 

1897. 

Post-mortem  examination. — None. 


CASE  XXXIV.— Male,  aged  46,  an  American  Judge,  seen  in  consultation  on 
5th  August  1895,  suffering  from  pernicious  anaemia. 

Duration. — 2  years. 

Apparent  cause. — Overwork  and  change  from  an  active  outdoor  to  a  sedentary 
indoor  life. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight 
(ij  st.);  anaesthesia,  stiffness  and  heaviness  in  the  legs  and  some  difficulty  in 
walking;  knee-jerks  absent;  red  corpuscles  markedly  diminished  in  number; 
alteration  in  shape  slight  ;  slight  poikilocytosis ;  heart's  action  very  feeble  ;  no 
retinal  haemorrhages  ;  urine  normal  in  colour  ;  no  albumen. 

Treatment. — Iron  and  arsenic  in  gradually  increasing  doses  was  advised. 

Immediate  result. — Some  improvement. 

Subsequent  progress. — Dr  Ewart  of  Eastbourne  has  kindly  sent  me  the 
following  notes  of  the  subsequent  progress  of  the  case  :— After  consulting  you 
he  went  to  Leamington  where,  without  advice,  he  took  the  waters,  but  says 
he  was  well,  only  feeling  weak.  He  then  ate  largely  of  fruit;  this  produced 
diarrhoea.  When  I  saw  him  a  month  afterwards,  he  was  extremely  anaemic 
and  very  weak,  unable  to  sit  up  for  more  than  half-an-hour  at  a  time.  On  the 
23rd  of  September  he  had  an  attack  of  faintness  so  severe  as  to  suggest  some 
internal  haemorrhage.  The  red  corpuscles  on  this  day  numbered  2,500,000  and 
the  haemoglobin  =  30  per  cent. ;  colour  index  .66  ;  the  leucocytes  were  unusually 
scanty;  the  red  corpuscles  were  very  variable  in  size,  some  large  and  pale, 
some  very  small,  some  oval,  pear-shaped  or  tailed. 

The  iron  and  arsenic  were  continued  and  3  ozs.  of  bone-marrow  and  3  ozs. 
of  raw  meat  in  each  24  hours,  added  on  24th  September.  He  took  the  bone- 
marrow  well  at  first,  but  had  no  appetite  for  any  other  food.  Drank  largely 
of  milk. 

On  5th  October,  he  looked  better,  but  could  not  take  the  bone-marrow, 
though  it  was  tried  in  various  ways.  Troublesome  diarrhoea  developed  and  the 
arsenic  (he  had  been  taking  five  drops  of  the  liquor)  had  to  be  discontinued. 
Food  confined  to  Benger  and  arrowroot ;  and  astringents  (at  first  bismuth  and 
opium,  then  bismuth  and  coto)  were  prescribed. 

On  12th  October,  the  diarrhoea  was  better ;  arsenic  (2^  drops)  again  pre- 
scribed ;  has  lost  ground  ;  increased  on  15th  October  to  5  drops. 

18th  October. — Doing  very  well.  More  appetite;  eats  toast  and  bread 
which  he  could  not  do  before.  Tongue  looks  more  natural,  not  so  red.  Bowels 
act  daily;  no  diarrhoea.  Arsenic  increased  to  7  drops.  No  retinal  haemorrhages 
found.     Red   corpuscles   number    1,675,000;    haemoglobin  =  28   per   cent.;    no 


128  DISEASES   OF   THE   BLOOD. 

excess  of  leucocytes  ;  there  are  many  megalocytes,  microcytes  and  poikilo- 
cytosis.  Patient  to-day  began  Benger,  extract  of  bone-marrow  (3i  twice  a  day) 
with  one  drachm  of  Dr  Pfeiffer's  haemoglobin. 

22nd  October. — Arsenic  increased  to  10  drops. 

4th  November. — Patient  is  making  no  progress  ;  sometimes  wanders  in  his 
conversation;  arsenic  increased  to  12  drops  daily;  and  on  7th  November  to 
15  drops. 

8th  November. — Red  corpuscles  numbered  800,000  ;  haemoglobin  —  about 
15  to  20  per  cent.  ;  colour  index  1.1  ;  a  great  number  of  extraordinarily  large 
and  very  pale  red  corpuscles  present  in  the  blood. 

2 1  st  November. — Since  last  report  the  patient's  condition  varied  to  a  most 
remarkable  extent  from  time  to  time.  At  the  morning  visit  he  was  often  found 
insensible,  stertorous,  and  to  all  appearance  at  the  point  of  death.  In  the 
evening  he  would  say  he  was  "  first  rate,"  but  though  he  often  appeared  clear 
and  asked  rational  questions,  he  could  never  sustain  a  conversation. 

Ultimate  result. — On  22nd  November  he  was  taken  to  Southampton  and 
shipped  for  America.     He  died  before  reaching  New  York. 

Post-mortem  examination. — None. 

CASE  XXXV.— Male,  aged  72,  seen  in  consultation  on  28th  August  1896, 
suffering  from  profound  anaemia  and  spinal  symptoms. 

Duration. — Several  months. 

Apparent  cause.— None. 

Symptoms. — Marked  anaemia  and  debility  ;  some  loss  of  weight  ;  numbness 
and  loss  of  power  in  the  legs  ;  absence  of  knee-jerks  ;  considerable  muscular 
atrophy  both  in  legs  and  thighs  ;  at  first,  no  affection  of  the  bladder  or  rectum  ; 
blood  not  examined  ;  occasional  diarrhoea. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  reached, 
9  drops  daily) ;  strychnine,  massage  and  the  faradic  current. 

Immediate  result. — Slight  temporary  improvement  as  regards  the  anaemia  ; 
no  improvement  in  the  spinal  symptoms. 

Subsequent  progress  and  Ultimate  result. — Increase  of  the  paralysis  ; 
paralysis  of  the  bladder  and  rectum  ;  death,  three  months  after  consultation. 

Post-mortem  examination. — None. 


CASE  XXXVI. — Female,  aged  50,  married  woman,  seen  in  consultation  on 
18th  September  1895,  suffering  from  profound  pernicious  anaemia. 

Duration. — 9  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  no  loss  of  weight  (patient  was 
a  very  stout  woman)  ;  shortness  of  breath  and  palpitation  ;  heart  sounds  very 
feeble  ;  venous  hum  in  neck  ;  blood  not  examined  ;  slight  jaundice  ;  urine  dark 
coloured  ;  occasional  vomiting  ;  tongue  pale,  smooth  and  moist. 

Treatment. — Arsenic  and  iron  in  gradually  increasing  doses  prescribed,  but 
patient  refused  to  take  the  medicine. 

Result. — Her  medical  attendant  wrote  me  that  "  the  patient's  strength  gradu- 
ally but  steadily  declined.  She  was  very  self-willed  and  refused  to  take  any 
medicine  on  the  plea  that  everything  made  her  sick.  She  died  exactly  a  month 
after  you  saw  her." 

Post-mortem  examination. — None. 


PERNICIOUS   AN/EMIA.  1 29 

CASE  XXXVII. — Male,  aged  71,  seen  in  consultation  on  16th  March  1893, 
suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility ;  shortness  of  breath  on  exertion; 
palpitation;  swelling  of  feet;  slight  jaundice  ;  red  corpuscles  greatly  diminished 
in  number  ;  many  megalocytes  and  microcytes  ;  marked  poikilocytosis ;  appa- 
rent nucleation  of  red  corpuscles ;  venous  hum  in  neck ;  heart's  action  feeble  ; 
somewhat  dilated  ;  systolic,  pulmonary  and  mitral  murmurs  ;  retinal  haemor- 
rhages ;  occasional  vomiting  and  diarrhoea. 

Iron  had  been  given  for  some  time  without  benefit. 

Treatment. — Arsenic  in  increasing  doses  was  prescribed  (maximum  dose 
reached,  2  or  3  drops)  ;  larger  doses  produced  vomiting. 

Immediate  result. — The  patient  improved  remarkably  for  a  time  ;  the  dropsy 
of  legs  disappeared  ;  able  to  get  about. 

Subsequent  progress  and  Ultimate  result. — Relapsed  in  September  and  finally 
died  on  17th  November  1893. 

Post-mortem  examination. — None. 

CASE  XXXVIII. — Female,  aged  58,  single,  shopkeeper,  seen  in  consultation 
June  1892,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility ;  some  loss  of  weight ;  shortness 
of  breath  on  exertion  ;  palpitation  ;  no  opportunity  of  examining  the  blood  ; 
venous  hum  in  neck;  heart's  action  feeble;  systolic,  mitral  and  pulmonary 
murmurs  ;  retinal  haemorrhages  ;  occasional  vomiting ;  slight  jaundice  ;  urine 
dark,  no  albumen. 

Treatment. — Arsenic  in  gradually  increasing  doses  ;  and  iron  (maximum  dose 
of  arsenic  reached  ?). 

Immediate  result. — Decided  improvement. 

Ultimate  result.  —  Relapse  ;  death  a  year  after  consultation. 

Post-mortem  examination. — None. 

CASE  XXXIX. — Male,  aged  67,  ironmonger,  seen  in  consultation  on  9th 
January  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — Dyspepsia  and  diarrhoea  (doubtful  if  diarrhoea  the  cause 
or  consequence). 

Symptoms. — Profound  anaemia  and  debility;  considerable  loss  of  weight; 
shortness  of  breath  and  palpitation  on  exertion ;  loud  venous  hum  in  neck  ; 
systolic  murmur  at  base  of  heart,  loudest  in  aortic  area ;  red  corpuscles  markedly 
diminished  in  number  ;  many  megalocytes  and  microcytes  ;  marked  poikilo- 
cytosis ;  lymphocytes  in  excess  ;  retinal  haemorrhages  ;  some  swelling  of  feet  ; 
frequent  vomiting  and  diarrhoea ;  tongue  very  smooth  and  moist  ;  slight 
jaundice  ;  urine  of  normal  colour  ;  no  albumen. 

Treatment. — Arsenic  in  gradually  increasing  doses  prescribed,  but  patient 
could  only  take  very  small  doses  because  of  gastric  irritation  (maximum  dose 
reached,  9  drops  daily  and  that  only  for  a  few  days)  ;  bone-marrow  and  iron 
subsequently  tried  ;  oxygen  inhalations  advised,  but  patient  refused  to  have  it. 

Result. — No  improvement ;  patient  died  on  12th  February  1898. 

Post-mortem  examination. — None. 

I 


130  DISEASES   OF   THE   BLOOD. 

CASE  XL. —  Male,  aged  2>7,  pitman,  admitted  to  Edinburgh  Royal  Infirmary 
on  16th  April  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — 2  years  ;  worse  for  3  or  4  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight  (1^ 
stone)  ;  shortness  of  breath  and  palpitation  on  exertion;  great  giddiness,  head- 
ache and  buzzing  in  the  ears  ;  slight  swelling  of  the  face  ;  occasional  vomiting  ; 
frequent  diarrhoea;  occasional  chilly  feelings  (rigors);  red  corpuscles  numbered 
1,200,000;  haemoglobin  =  44  per  cent.;  white  corpuscles  numbered  3,400;  on 
microscopical  examination,  a  few  megalocytes,  many  microcytes,  moderate 
poikilocytosis,  apparent  nucleation  of  red  corpuscles,  some  truly  nucleated  red 
corpuscles  ;  excess  of  lymphocytes  ;  blood  plates  less  numerous  than  normal ; 
retinal  haemorrhages  ;  slight  jaundice  ;  urine  dark,  containing  a  marked  excess 
of  indican  and  an  enormous  excess  of  combined  sulphates  ;  large  uric  acid 
deposits  ;  no  albumen  ;  considerable  pigmentation  of  the  skin  (patient  sent  to 
hospital  as  a  case  of  Addison's  disease). 

Treatment. — Arsenic  in  gradually  increasing  doses  and  salicylate  of  bismuth 
for  diarrhoea  ;  bone-marrow,  oxygen  inhalations,  etc.  Maximum  dose  of  arsenic 
reached,  63  drops  daily. 

Immediate  result. — Marked  temporary  improvement,  after  the  arsenical  treat- 
ment was  pushed. 

Subsequent  progress  of  the  case. — On  24th  May,  the  patient  looked  and  felt 
very  much  better. 

On  28th  May,  he  began  to  complain  of  itchiness  of  the  eyeballs  and  pain  in 
the  stomach ;  the  dose  of  arsenic  was  therefore  reduced. 

Towards  the  end  of  June,  pains,  numbness  and  anaesthesia  in  the  feet,  legs, 
arms,  and  hands,  obviously  due  to  peripheral  neuritis,  developed,  and  the  knee- 
jerks  became  abolished.  The  arsenic  was  consequently  stopped  ;  strychnine  was 
prescribed,  together  with  phenacetin  and  morphia  for  the  relief  of  the  pains. 

4th  July. — Bone-marrow  tabloids  prescribed. 

7th  July. — The  anaemia  has  become  more  marked  since  the  arsenic  was 
stopped  ;  the  eyes  are  still  sore,  and  the  pains  in  the  feet  severe,  especially  at 
night. 

22nd  July. — More  anaemic  ;  skin  desquamating ;  pains  less,  but  anaesthesia 
in  feet  and  hands  more  marked. 

30th  July. — Temperature  went  up  to  1040 ;  pulse  rapid  (100)  and  dicrotic; 
anaemia  more  marked  ;  urine  very  dark ;  very  prostrate  ;  fresh  retinal  haemor- 
rhages ;  arsenic  recommenced  (10  minims  daily). 

3rd  August. — Very  anaemic,  feeble  and  emaciated ;  looks  very  much  as  he 
did  at  the  time  of  his  admission  to  hospital ;  tongue  dry  ;  very  thirsty.  Fresh 
bone-marrow  mixed  with  mashed  potato  prescribed. 

10th  August. — Patient  died  at  10  p.m. 


PERNICIOUS   AN/EMIA.  131 

The  following:  table  shows  the  condition  of  the  blood  at  different  dates  : — 


Date. 

Red 
Corpuscles. 

Haemoglobin. 

Colour  Index 
(Corrected). 

White 
Corpuscles. 

1 8th  April 

1,200,000 

44  per  cent. 

2. 

3,438 

27th    „ 

8l6,000 

28       „ 

i-9 

4,370 

29th     „ 

975,000 

30       „ 

i-7 

3,125 

10th  May 

1,234,000 

38       „ 

i-7 

5,312 

18th      „ 

1,600,000 

44       „ 

i-5 

3,125 

23rd      „ 

1,670,000 

62       „ 

2. 

2,190 

2nd    June 

1,366,700 

60       „ 

2.6 

5,156 

14th      „ 

1,683,334 

62       „ 

2. 

1,600 

20th      „ 

1 

1,416,667 

60       ,, 

2.3 

2,223 

28th      „ 

1,350,000 

5°      „ 

2, 

4,531 

4th    July 

1,475,000 

43      „ 

i-4 

2,600 

1 2th       „ 

I?333>334 

30      „ 

1.2 

3,500 

22nd     „ 

940,000 

32       „ 

i-9 

4,700 

29th      „ 

642,000 

24      „ 

2.1 

2,IOO 

5th  August 

370,000 

16       „ 

2.4 

1,900 

Post-mortem  examination. — Made  by  Dr  Fleming  on  12th  August,  at  1  p.m. 
The  appearances  were  typical  of  uncomplicated  pernicious  anaemia. 

Body  somewhat  emaciated  and  very  anaemic.  Both  pleura  uniformly  ad- 
herent ;  the  lungs  weighed  1  lb.  4  ozs.  and  1  lb.  9  ozs.  respectively,  and  were 
markedly  cedematous  ;  a  few  old  tubercles  in  the  upper  lobe  of  the  right  lung. 
The  heart  and  great  vessels  contained  very  little  blood ;  the  heart  weighed 
15  ozs.,  and  was  very  fatty.  The  liver  weighed  3  lbs.  5  ozs.,  was  very  fatty,  and 
contained  a  large  excess  of  iron.  The  spleen  weighed  8  ozs.,  and  gave  no  iron 
reaction.  The  kidneys  weighed  4  ozs.  and  5  ozs.  respectively;  they  were  markedly 
fatty  and  did  not  give  the  iron  reaction.  The  suprarenal  capsules  were  normal. 
The  mucous  coat  of  the  stomach  was  atrophied  ;  the  mucous  and  submucous 
coats  of  the  upper  end  of  the  small  intestine  were  cedematous  and  bile-stained  ; 
some  of  the  coils  of  the  intestine  were  bound  together  by  old  adhesions  ;  there 
was  no  ulceration  of  the  intestines.  The  brain  was  markedly  anaemic.  The 
spinal  cord  was  anaemic,  but  otherwise  normal  to  the  naked  eye.  The  peripheral 
nerves  were  normal  to  the  naked  eye.  The  marrow  of  the  bones  was  of  a  deep 
purple  colour.     A  few  very  minute  petechial  hemorrhages  were  present  on  the 


132  DISEASES   OF   THE   BLOOD. 

peritoneal  surface  of  the  stomach  ;  there  were  several  retinal  haemorrhages,  but 
no  petechial  haemorrhages  elsewhere. 

The  microscopical  examination  of  the  organs  and  tissues  has  not  yet  been 
completed. 


CASE  XLI. — Male,  aged  51,  clergyman,  seen  in  consultation  on  25th  April 
1892,  suffering  from  profound  pernicious  anaemia. 

Duration. —  1  year. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility ;  some  loss  of  weight ;  shortness 
of  breath  on  exertion,  palpitation,  slight  swelling  of  feet ;  red  corpuscles  markedly 
diminished  in  number  ;  many  megalocytes  and  microcytes ;  marked  poikilo- 
cytosis  ;  systolic  pulmonary  and  mitral  murmurs  ;  venous  hum  in  the  neck  ;: 
retinal  haemorrhages  ;  bowels  constipated  (diarrhoea  9  months  ago)  ;  frequent 
vomiting  ;  urine  normal  in  colour,  no  albumen. 

Treatment. — Advised  to  increase  the  dose  of  arsenic  which  he  has  been 
taking  (maximum  dose  reached,  5  drops  three  times  daily) ;  rest  in  bed ;. 
strychnine. 

Result. — Died  eight  days  after  consultation. 

Post-mortem  examination. — None. 


CASE  XLII. — Married  woman,  aged  31,  admitted  to  Edinburgh  Royal  In- 
firmary on  9th  June  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — 3^  months. 

Apparent  cause. — Pregnancy.  Always  enjoyed  good  health  until  the  present 
illness  commenced.  Has  been  married  nine  years  and  has  had  five  children. 
The  anaemia  developed  when  she  was  6^  months  pregnant,  without  apparent 
cause,  and  has  gradually  increased.  Was  delivered  at  the  full  term,  on  24th 
May  1898  ;  labour  easy  ;  no  loss  of  blood.  For  a  week  after  confinement,, 
improved  slightly  ;  then,  got  rapidly  worse. 

Symptoms. — Very  profound  anaemia  and  debility;  no  jaundice;  great  short- 
ness of  breath  ;  frequent  palpitation  ;  no  swelling  of  the  feet  (they  were  swollen 
before  her  confinement) ;  face  slightly  swollen  ;  some  dulness  and  fine  crepita- 
tions over  the  base  of  each  lung  ;  systolic,  mitral,  and  pulmonary  murmurs  ; 
venous  hum  in  the  neck;  temperature  104.80;  pulse  146;  respirations  44;  occa- 
sional vomiting  ;  no  diarrhoea  ;  urine  pale  and  free  from  albumen  ;  a  scanty  and 
rather  foetid  vaginal  discharge  ;  tongue  pale  and  dry;  very  thirsty ;  innumerable 
very  small  haemorrhages  scattered  over  both  retinae,  and  a  few  flame-like  haemor- 
rhages at  the  margins  of  the  discs  ;  red  corpuscles,  780,000  per  cm.  (blood 
obtained  from  bandaged  finger,  simple  puncture  of  the  finger  and  ear  yielding 
no  blood);  haemoglobin  =  20  per  cent.;  colour  index  =1.4;  white  corpuscles 
numbered  6,250  per  cm. ;  many  megalocytes  and  microcytes,  marked  poikilo- 
cytosis. 

Treatment. — Arsenic,  oxygen  inhalations,  strychnine,  and  digitalis. 

Result. — For  two  days  some  improvement  ;  then  oedema  of  the  lungs  sud- 
denly developed,  and  the  patient  died  on  14th  June — five  days  after  admission. 

Post-mortem  examination. — Made  by  Dr  Fleming  on  15th  June,  at  1  P.M. 
The  appearances  were  typical  of  uncomplicated  pernicious  anaemia  ;  there  was. 
no  puerperal  septic  condition. 

Body  well  nourished  and  very  bloodless.    The  right  pleural  cavity  contained. 


PERNICIOUS   AN/EMIA.  133 

15  ozs.,  the  left  17  ozs.,  and  the  pericardial  sac  4^  ozs.  of  clear  serous  fluid.  The 
.heart  weighed  14  ozs. ;  it  was  covered  with  a  thick  layer  of  fat  ;  the  muscle  was 
in  an  advanced  condition  of  fatty  degeneration.  The  lungs  weighed  1  lb.  15  ozs. 
and  1  lb.  9  ozs.  respectively  ;  both  were  markedly  cedematous  ;  at  the  apex  of 
the  right,  the  pleura  was  adherent,  the  lung  puckered  and  the  seat  of  some 
•old  (healed)  tubercles.  The  liver  weighed  5  lbs.  4  ozs.  ;  it  was  very  fatty  and 
gave  a  very  marked  iron  reaction.  The  spleen  weighed  1  lb.  ;  its  capsule  was 
thickened,  its  tissue  soft  and  congested  ;  it  gave  a  marked  iron  reaction.  The 
kidneys  weighed  7  ozs.  and  y\  ozs.  respectively  and  were  somewhat  fatty  and 
affected  with  cloudy  swelling.  The  mucous  membrane  of  the  stomach  presented 
a  mammillated  appearance  towards  the  pyloric  end  ;  it  was  elsewhere  atrophied 
(apparently  the  result  of  post-mortem  change) ;  the  mucous  and  submucous  coats 
of  the  upper  end  of  the  small  intestine  were  cedematous  and  bile-stained.  The 
uterus  was  enlarged  ;  its  cavity,  which  measured  3  inches  in  length,  contained  a 
small  quantity  of  partly  adherent  broken-down  blood  clot  which  was  not  septic. 
The  brain  weighed  2  lbs.  14  ozs.  and  was  pale  and  somewhat  cedematous.  The 
retince  contained  numerous  small  haemorrhages  ;  there  were  no  petechial  haemor- 
rhages in  other  parts  of  the  body.  The  spinal  cord  was  anaemic,  but  otherwise 
normal  to  the  naked  eye.  The  bone-marrow  was  of  a  deep  purple  colour,  highly 
characteristic  of  the  disease. 

Microscopical  examination  not  yet  completed. 


CASE  XLIII. — Female,  widow,  aged  65,  seen  in  consultation  on  23rd  May 
1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months. 

Apparent  cause. — Patient  herself  blames  mental  worry;  a  year  ago  she  began 
to  be  troubled  with  sore  gums  (inflammation  of  the  gums,  buccal  mucous  mem- 
brane and  side  of  the  tongue). 

Symptoms. — Profoundly  anaemic  and  debilitated;  considerable  loss  of  weight; 
very  short  of  breath  ;  frequent  palpitation  ;  throbbing  in  the  head  ;  some  swell- 
ing of  the  feet ;  slight  swelling  of  the  face ;  occasional  headache ;  very  occasional 
vomiting;  no  diarrhoea;  no  jaundice;  skin  of  a  yellow  lemon  tint;  urine  pale, 
contains  a  small  quantity  of  albumen  ;  retinal  haemorrhages  ;  for  the  past  two 
days  has  had  some  (slight)  epistaxis.  The  condition  of  the  blood  (which  was 
examined  by  Dr  Robert  Muir)  was  as  follows  :  —  Red  corpuscles  number 
1,328,000;  many  megalocytes  and  microcytes ;  marked  poikilocytosis  ;  haemo- 
globin==32  per  cent.;  colour  index— 1.2;  leucocytes  much  diminished — 2,000; 
blood  plates  much  diminished — about  20,000  ;  a  few  truly  nucleated  red  cor- 
puscles of  moderate  size  with  homogeneous  nucleus  staining  very  deeply  ;  the 
relative  proportion  of  lymphocytes  was  slightly  increased;  there  were  no 
myelocytes. 

Treatment. — Rest  in  bed  and  arsenic  in  gradually  increasing  doses  prescribed. 

Result. — Patient  could  not  take,  or  would  not  take,  the  arsenic  and  other 
remedies  (bone-marrow,  strychnine,  digitalis,  etc.)  which  were  from  time  to  time 
prescribed. 

10th  June  1898. — Patient  much  worse  ;  temperature  last  night  102°  ;  looks 
extremely  ill  ;  face  more  swollen  ;  arsenic  to  be  given  unknown  to  the  patient, 
and  if  it  does  not  agree,  transfusion  advised.  (Only  one  dose,  5  drops,  of  arsenic 
given,  as  it  was  followed  by  vomiting.) 

1 2th  June. — Patient  transfused  (four  ounces  of  blood  with  four   ounces    of 


134  DISEASES   OF   THE    BLOOD. 

phosphate  of  soda  solution) ;  bore  the  operation  very  well  ;  same  afternoon 
became  unconscious  ;  rallied  under  stimulants  and  then  steadily  improved 
for  three  weeks. 

5th  July  1898. — Blood  counted  by  Dr  Muir.  Red  corpuscles  =  1,050,000  ; 
haemoglobin =28  per  cent. 

9th  July  1S98. — Looks  very  much  worse  ;  has  run  down  very  rapidly  during 
the  past  two  or  three  days  ;  temperature  102. 40  ;  face  more  swollen  ;  slightly 
jaundiced  ;  urine  dark. 

As  transfusion  undoubtedly  produced  temporary  benefit,  advised  that  should 
be  transfused  again  and  the  operation  regularly  repeated  at  short  intervals,  and 
not  delayed  until  its  beneficial  effects  have  passed  off. 

1 2th  July. — Again  transfused,  but  the  operation  unsuccessful  (the  boy  who 
was  giving  the  blood  fainted  and  the  transfusion  had  to  be  stopped). 

27th  July. — Transfusion  again  performed,  most  successfully  ;  for  some  days 
was  followed  by  shortness  of  breath  ;  after  this  the  patient  improved  considerably. 

12th  August. — Looks  very  much  better  and  more  vigorous  ;  lips  and  tongue 
have  more  colour  ;  conjunctivas  still  very  bloodless  and  slightly  yellow ;  face  less 
swollen  ;  is  eating  very  well ;  says  she  feels  greatly  better  ;  is  very  bright  and 
talkative. 

Advised  to  be  again  transfused  and  the  operation  to  be  regularly  repeated  at 
short  intervals.     My  recommendation  was  not  carried  out. 

Her  medical  attendant  informs  me  that  she  remained  pretty  well  until  the 
end  of  September,  when  the  mouth  again  became  irritable.  During  the  second 
week  in  October  another  relapse  took  place.  She  was  again  transfused  on  16th 
October  ;  the  operation  was  followed,  as  on  previous  occasions,  by  a  rigor  and 
rise  of  temperature  (1030  F.). 

1st  November. — Patientagain  seen  to-day ;  looks  verymuch  worse  ;  profoundly 
anaemic  ;  much  thinner  ;  several  petechial  haemorrhages  on  the  surface  of  the 
tongue,  buccal  mucous  membrane  and  lower  extremities  ;  feet  more  swollen  ; 
hands  slightly  swollen  ;  urine  dark  and  containing  a  small  quantity  of  albumen  ; 
the  temperature,  which  for  some  days  after  the  last  transfusion  was  con- 
siderably elevated,  is  again  normal  ;  for  the  past  two  days  a  good  deal  of 
wandering  ;  since  last  visit  had  an  attack  of  diarrhoea. 

The  question  of  renewed  transfusion  again  considered.  It  was  decided,  as 
the  patient  would  certainly  die,  probably  in  the  course  of  a  few  days,  if  nothing 
was  done,  to  recommend  that  transfusion  should  be  again  tried  ;  and  that,  if 
improvement  should  again  result,  the  operation  should  be  repeated  at  short 
intervals  and  at  the  time  when  the  improvement  is  most  marked.  This  was  the 
course  which  I  had  previously  advised.  It  seems  useless  to  transfuse  and  after 
improvement  has  taken  place  to  wait  until  the  patient  has  again  relapsed  before 
repeating  the  operation.  If  atiy  permanent  benefit  is  to  be  obtained  in  severe 
cases  of  pernicious  ana  mia  from  transfusion  the  operation  ought,  i?i  my  opinion, 
to  be  repeated  at  short  intervals  and  to  be  performed  when  the  patie?it  is  at  the 
height  of  the  improvement  curve  ;  it  is  only,  I  think,  in  this  way  that  permanent 
benefit  can  possibly  be  expected,  for  the  beneficial  effect  of  a  single  transfusion 
seems  to  pass  off  in  the  course  of  a  few  weeks.  In  this  particular  case,  there  was 
liitle  improvement  for  the  first  week  after  the  operation  ;  the  patient  then  slowly 
improved  (after  every  operation  except  the  last),  for  three  or  four  weeks,  and 
then  again  got  rapidly  worse.  In  this  particular  case,  the  operation  ought,  I 
think,  to  be  repeated  every  three  weeks. 


PERNICIOUS   AN/EMIA. 


135 


CASE  XLIV. — Married  woman,  aged  44,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  16th  June  1898. 

Duration. — 12  months  ;  worse  for  the  past  5  months. 

Apparent  cause. — None. 

Symptoms. — Profound  anaemia  and  debility  ;  considerable  loss  of  weight 
(used  to  be  very  fat)  ;  shortness  of  breath ;  palpitation  ;  slight  swelling  of  feet 
and  face  ;  slight  yellowness  of  conjunctivae  ;  areolae  of  the  nipples  very  dark 
(this  is  quite  recent) ;  no  pigmented  patches  on  buccal  mucous  membrane  ; 
systolic,  mitral,  and  pulmonary  murmurs  ;  venous  hum  in  the  neck  ;  some 
giddiness  ;  beating  in  the  head  ;  some  headache  ;  no  retinal  haemorrhages  (but 
they  developed  before  death) ;  temperature  on  admission  normal  (subsequently 
became  elevated) ;  very  occasional  vomiting  ;  no  diarrhoea  ;  tongue  clean  and 
moist,  not  abnormally  smooth;  red  corpuscles  number  1,160,000,  rouleaux 
formation  imperfect ;  a  few  megalocytes  and  microcytes  and  comparatively 
slight  poikilocytosis  (the  alterations  in  the  size  and  shape  of  the  red  corpuscles 
much  less  marked  than  in  most  cases  of  profound  pernicious  anaemia) ;  haemo- 
globin =34  per  cent. ;  colour  index  =  1.4  ;  white  corpuscles  number  3,438  (50  per 
cent,  being  multinucleated  and  50  per  cent,  being  uninucleated) ;  some  apparent 
nucleation  of  the  red  corpuscles  ;  no  true  nucleation  seen ;  urine  amber-coloured 
(subsequently  became  dark);  no  albumen  ;  heavy  phosphatic  cloud. 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  reached  = 
45  drops  per  day),  bone-marrow,  oxygen  inhalations  ;  strychnine,  strophanthus. 

Result. — For  a  short  time  there  was  slight  (but  very  slight)  improvement ;  as 
the  result  of  the  large  doses  of  arsenic  peripheral  neuritis  (pains  in  the  hands, 
feet,  arms  and  legs,  tingling,  numbness  and  loss  of  the  knee-jerks)  developed. 
The  arsenic  was  consequently  stopped.  After  this,  notwithstanding  the  adminis- 
tration of  bone-marrow,  oxygen  inhalations,  strychnine,  strophanthus,  &c,  the 
patient  rapidly  got  worse  ;  oedema  of  the  lungs  developed  ;  and  she  died  on  30th 
July.  The  temperature  rose  repeatedly  above  the  normal  during  her  stay  in 
hospital  and  the  urine  became  very  dark  in  colour. 

The  condition  of  the  blood  is  shown  in  the  following  table  : — 


Date. 

Red 

Corpuscles. 

Haemoglobin. 

Colour  Index 
(Corrected) 

White 
Corpuscles. 

17th  June 

1 ,  1 60,000 

34  per  cent. 

1.4 

3,438 

24th    „ 

900,000 

3°       » 

1.6 

3,000 

1st     July 

1,541,500 

32       „ 

1. 

3,755 

8th        „ 

1,158,333 

36       „ 

1.6 

2,000 

17th      „ 

841,700 

20       „ 

1.2 

1,600 

22nd     ,, 

660,000 

20       „ 

i-5 

1,100 

29th      „ 

459,000 

14       „ 

i-5 

1,900 

Post-mortem  examination. — Made  by  Dr  Fleming  on  31st  July.    The  appear- 
ances were  in  every  respect  typical  of  pernicious  anaemia. 


136  DISEASES   OF   THE    BLOOD. 

The  body  was  fairly  well  nourished  and  very  bloodless  ;  there  was  slight 
oedema  of  the  feet  and  legs.  The  pericardial  sac  contained  1  oz.  of  clear  serum  ; 
the  pleural  cavities  were  obliterated  by  old  adhesions.  There  were  several  small 
petechial  haemorrhages  on  the  surface  of  the  heart,  stomach,  and  dura  mater. 
The  heart  weighed  13  ozs. ;  it  was  covered  with  a  considerable  layer  of  yellow 
fat  ;  its  cavities  were  empty  ;  its  muscle  in  an  advanced  stage  of  fatty  degenera- 
tion. The  right  lung  weighed  1  lb.  8  ozs.  and  the  left  1  lb.  1  oz.,  and  were 
markedly  cedematous.  The  liver  weighed  3  lbs.  5  ozs.,  was  markedly  fatty,  and 
gave  a  very  marked  iron  reaction.  The  spleen  weighed  1 1  ozs.  and  was  of  a 
deep  purple  colour  ;  it  gave  no  iron  reaction.  The  kidneys  weighed  6  ozs.  and 
7  ozs.  respectively,  and  gave  a  slight  iron  reaction  ;  the  tissue  was  soft,  some- 
what fatty,  and  presented  slight  interstitial  change.  The  stomach  was  healthy  ; 
its  mucous  membrane  was  somewhat  thin  (?  post-mortem  change).  The  mucous 
and  submucous  coats  of  the  upper  end  of  the  small  intestine  were  cedematous 
and  bile-stained,  but  otherwise  normal.  The  suprarenal  capsules  were  normal. 
The  brain  weighed  2  lbs.  12^  ozs.  and  was  markedly  anaemic.  The  spinal  cord 
was  markedly  anaemic,  but  otherwise  normal  to  the  naked  eye.  The  peripheral 
nerves  were  normal  to  the  naked  eye.  The  retina;  contained  several  recent 
haemorrhages. 

The  microscopical  examination  has  not  been  completed. 


CASE  XLV.— Male,  aged  58,  mast-maker,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  16th  June  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — 18  months. 

Apparent  cause. — Patient  attributes  his  illness  to  mental  worry  and  overwork  ; 
has  suffered  from  bleeding  piles  for  12  years,  bleeding  at  times  very  profuse, 
but  little  or  none  for  the  past  year.  At  the  beginning  of  the  present  illness,  he 
suffered  from  gastric  catarrh  ;  throughout  this  illness,  the  bowels  have  been 
constipated. 

Symptoms. — Profound  anaemia  and  debility;  skin  lemon  yellow  coloured; 
considerable  loss  of  weight ;  very  short  of  breath  on  exertion  ;  frequent  palpita- 
tion ;  appetite  poor ;  very  thirsty  ;  occasional  vomiting  ;  no  diarrhoea  ;  bowels 
constipated  ;  tongue  slightly  furred  and  rather  dry  ;  some  oedema  of  feet,  face 
and  body  generally  ;  some  yellow  tinging  of  conjunctiva  ;  venous  hum  in  the 
neck  ;  heart  sounds  very  feeble  ;  pulse  markedly  jerking  in  character  ;  no  pul- 
monary systolic  murmur  ;  urine  markedly  pale  and  free  from  albumen  :  no 
retinal  haemorrhages  ;  a  few  minute  petechiae  on  the  wrists  and  legs  ;  blood 
highly  characteristic;  red  corpuscles  number  642,000;  haemoglobin  =  16  per 
cent.;  colour  index=i.4;  white  corpuscles  number  2,500  (uninuclcated  50  per 
cent.,  multinucleated  50  per  cent.)  ;  blood  plates  much  diminished  in  number); 
many  megalocytes  of  large  size  ;  many  microcytes  ;  very  marked  poikilocytosis; 
much  apparent  nucleation  ;  some  truly  nucleated  red  corpuscles;  no  micro- 
organisms (stained  films  and  incubated  gelatine  tubes). 

Treatment. — Arsenic  in  gradually  increasing  doses  (maximum  dose  reached, 
42  drops  per  diem) ;  laxatives. 

Result. — Felt  better  after  a  free  evacuation  of  bowels,  but  no  real  improve- 
ment. 

On  3rd  July,  oedema  of  the  lungs  suddenly  developed  and  the  patient  died 
on  4th  July. 


PERNICIOUS   ANAEMIA.  137 

The  condition  of  the  blood  at  different  dates  is  shown  in  the  following  table  : — 


Date. 

Red 

Corpuscles. 

Haemoglobin. 

Colour  Index 
(Corrected). 

White 
Corpuscles. 

17th  June 
24th      „ 
1st  July 

642,000 
650,000 
542,000 

16  per  cent. 
20       „ 
20       „ 

1.4 

1.6 

2.2 

2,500 

3,125 
4,000 

Post-mortem  examination. — Made  by  Dr  Fleming  on  5th  July. 

Body  very  anaemic,  somewhat  emaciated  ;  slight  cedema  of  the  legs  ;  a  few 
minute  petechial  haemorrhages  on  the  hands  and  trunk.  The  left  pleural  cavity 
■contained  40  ozs.,  the  right  45  ozs.,  and  the  pericardium  1 1  ozs.  of  clear  serum. 
The  heart  weighed  11  ozs. ;  the  endocardium  and  chordae  tendineae  were  slightly 
thickened  ;  the  muscular  substance  presented  no  evidence  to  the  naked  eye  of 
fatty  degeneration,  but  was  in  a  marked  condition  of  brown  atrophy.  The  lungs 
weighed  1  lb.  7  ozs.  and  r  lb.  6  ozs.  respectively;  the  upper  lobes  were  markedly 
emphysematous,  the  lower  lobes  markedly  cedematous.  The  liver  weighed  3  lbs. ; 
it  presented  little  or  no  evidence  of  fatty  degeneration  to  the  naked  eye  and  gave 
a  slight  (blue)  reaction  to  the  iron  test.  The  spleen  weighed  9  ozs.  ;  it  gave  a 
slight  iron  reaction.  The  kidneys  weighed  6  ozs.  and  5  ozs.  respectively,  both 
showed  decided  interstitial  change,  but  gave  no  iron  reaction.  The  suprarenal 
capsules  were  normal.  A  few  minute  petechial  haemorrhages  on  the  outer 
surface  of  the  stomach;  the  mucous  membrane  was  for  the  most  part  atrophied  ; 
near  the  pylorus  there  were  about  six  mammillated  projections.  A  few  minute 
haemorrhages  on  the  outer  surface  of  the  small  intestine  (jejunum) ;  mucous  and 
submucous  coats  cedematous  and  bile-stained,  no  ulceration.  Bone-marrow  of 
a  dark  purple  colour,  highly  characteristic  of  pernicious  anaemia.  The  brain 
weighed  3  lbs.  4  ozs.,  and  was  very  anaemic  and  cedematous.  There  were  no 
haemorrhages  in  the  retina. 

The  microscopical  examination  of  the  tissues  and  organs  not  yet  completed. 

Note. — In  this  case,  in  which  the  clinical  symptoms  and  the  condition  of  the 
blood  were  most  typical,  and  the  disease  of  long  (18  months)  duration,  there  was 
no  fatty  degeneration  of  the  heart  and  the  liver  only  contained  a  slight  excess  of 
iron,  as  determined  by  the  ferrocyanide  test. 

CASE  XLVI. — Male,  aged  48,  estate  manager,  seen  in  consultation  on  25th 
March  1897,  suffering  from  profound  anaemia  and  angina  pectoris. 

Duration. — Several  months. 

Apparent  cause. — None.  A  year  ago  the  patient  suffered  from  gouty  glyco- 
suria ;  he  was  strictly  dieted  and  lost  more  than  2  stone  in  weight ;  he  weighed 
at  that  time  i8|  stone.  For  several  months  past  he  has  been  losing  colour. 
During  the  past  three  months  the  anaemia  has  markedly  increased,  he  has 
become  very  breathless  on  exertion  and  has  had  several  attacks  of  severe  sub- 
sternal pain  (angina  pectoris). 

Symptoms. — Profound  anaemia  and  debility  ;  no  jaundice  ;  great  shortness 
of  breath  on  exertion  ;  occasional  severe  angina-like  pain  on  exertion  ;  frequent 
palpitation  ;  no  dropsy  ;  heart  slightly  dilated  ;  a  soft  systolic  murmur  in  the 
aortic  and  mitral  areas  ;  venous  hum  in  the  neck  ;  urine  free  from  albumen  and 


138  DISEASES   OF   THE   BLOOD. 

sugar  and  not  abnormally  dark  in  colour  ;  red  corpuscles  markedly  diminished 
in  number  ;  some  microcytes  and  megalocytes  ;  moderate  poikilocytosis  ;  no 
retinal  haemorrhages. 

Treatment. — Arsenic,  strychnine,  iron  (Blaud's  pill  capsules)  and  subse- 
quently bone-marrow  tabloids. 

Subsequent  progress  and  Result. — For  the  first  month  after  the  treatment  was 
commenced,  the  patient  improved  considerably.  The  stomach  then  became 
irritable  and  the  arsenic  had  consequently  to  be  diminished  and  then  altogether 
stopped  (the  maximum  dose  reached  was  9  drops  per  diem).  After  this  date, 
the  patient  rapidly  got  worse  and  died  some  two  months  after  he  first  came 
under  my  observation. 

CASE  XLVII. — Male,  aged  60,  clergyman,  was  seen  in  consultation  on  the  17th 
August  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — 18  months. 

Apparent  cause. — None. 

Symptoms. — Profound  debility  and  anaemia  ;  marked  loss  of  flesh  ;  tongue 
clean  and  smooth  ;  marked  shortness  of  breath  and  palpitation  on  exertion  ; 
heart's  action  very  feeble  ;  venous  hum  in  the  neck  ;  (no  opportunity  of  examin- 
ing the  blood);  no  retinal  haemorrhages;  no  diarrhoea;  no  vomiting;  urine  pale; 
occasional  attacks  of  fever. 

Treatment. — Has  been  treated  with  arsenic,  iron  and  bone-marrow.  For  a 
time  improved,  but  has  recently  again  relapsed.  Advised  to  continue  the  arsenic 
and  bone-marrow  in  gradually-increasing  doses  ;  and  if  there  is  no  improvement, 
the  question  of  transfusion  to  be  considered. 

Result. — No  improvement  ;  death  ten  days  after  first  seen. 

CASE  XLVIII. — Male,  aged  35,  veterinary  surgeon,  seen  in  consultation  on 
27th  September  1898,  suffering  from  profound  pernicious  anaemia. 

Duration. — Several  months  ;  worse  for  six  weeks. 

Apparent  cause. — None  ;  prior  to  the  commencement  of  the  present  illness 
was  an  extremely  robust,  active,  and  hard-working  man  ;  has  occasionally  over- 
indulged in  alcohol. 

Symptoms. — Profoundly  anaemic  and  debilitated,  has  fainted  on  getting  out 
of  bed  ;  has  lost  a  good  deal  of  weight,  but  is  still  well  covered  with  fat  ;  marked 
shortness  of  breath  and  palpitation  on  exertion  ;  conjunctivae  slightly  yellow  ; 
urine  extremely  pale  (a  specimen  made  in  my  presence)  and  has  been  so 
throughout  the  illness  ;  no  albumen  ;  soft  systolic  murmur  in  the  mitral,  pul- 
monary and  aortic  areas  ;  venous  hum  in  the  neck  ;  bowels  regular ;  diarrhoea 
a  month  ago,  said  to  be  due  to  purgative  medicine  ;  no  vomiting  ;  tongue  clean 
and  somewhat  dry;  very  thirsty;  gums  bleeding-  ;  a  few  petechial  haemorrhages 
under  the  tongue  and  on  the  neck  and  upper  part  of  the  trunk ;  double  optic 
neuritis  ;  numerous  retinal  haemorrhages,  some  flame-shaped,  round  the  discs, 
others  petechial  over  the  retina?  ;  a  few  yellowish- white  spots,  the  remains  of  former 
haemorrhages  in  the  retinae  ;  no  oedema  ;  blood  examined  by  medical  attendant — 
red  corpuscles  =  1,000,000  per  cubic  millimetre;  haemoglobin  not  estimated  ,-. 
moderate  degree  of  poikilocytosis  ;  temperature  for  some  weeks  persistently 
above  normal,  highest  point  reached  1030  F.;  no  evidence  of  disease  (except  the 
profound  anaemia  and  its  results)  in  any  of  the  organs  ;  knee-jerks  normal. 

Treatment. — Has  been  taking  arsenic  and  bone-marrow.  Advised  to  con- 
tinue these  remedies  in  increased  doses. 

Result. — Rapidly  got  worse  and  died  a  few  days  after  the  consultation. 


LEUCOCYTHAEMIA. 

Definition  or  Short  Description. — The  terms  leukcemia  (white 
blood)  and  leucocythcemia  (white -celled  blood)  are  applied  to  a 
condition  of  the  blood  in  which  the  white  blood  corpuscles  are 
greatly  increased  in  number,  both  (a)  absolutely  and  (b)  relatively 
to  the  red  cells  ;  while  the  red  blood  corpuscles  and  the  haemo- 
globin are  at  the  same  time  diminished  in  amount — often  con- 
siderably so.  In  other  words,  in  cases  of  leucocythaemia  there  is 
also  more  or  less,  and  sometimes  great,  anaemia. 

The  increase  of  the  white  cells  is  not  merely  temporary  as  it  is 
usually  in  leucocytosis.  Further,  in  leucocythaemia  the  increase  of 
the  white  corpuscles  is  for  the  most  part  due  to  the  presence  in  the 
blood  of  myelocytes  (spleno-medullary  form),  or  of  lymphocytes 
(lymphatic  form)  ;  whereas  in  leucocytosis  the  increase  of  the  white 
corpuscles  is  for  the  most  part,  or  entirely,  due  to  an  increase  of  the 
polymorpho-nuclear  form  of  white  corpuscles. 

Leucocythaemia  is  usually  a  chronic  condition,  which  is  slowly 
developed,  and  which  usually  progresses  more  or  less  steadily  to  a 
fatal  issue.  In  rare  cases,  the  disease  runs  a  rapid,  or  comparatively 
rapid,  course  {acute  leucocythcemia). 

In  most  cases  of  leucocythaemia  (but  especially  in  the  spleno- 
medullary  form)  the  spleen  is  greatly  enlarged  ;  in  other  cases 
(more  especially  in  the  lymphatic  variety)  the  lymphatic  glands 
are  enlarged.  In  the  great  majority  of  cases,  the  marrow  of  the 
bones  is  diseased  ;  and  it  is  now  generally  held  that  in  the  spleno- 
medullary  form  the  marrow  of  the  bones  is  in  all  probability  the 
primary  seat  of  the  lesion. 

Historical  Note. — Leucocythaemia  is  a  very  interesting  condi- 
tion. It  was  first  described  in  the  year  1845  by  the  late  Professor 
Hughes  Bennett  as  a  primary  suppuration  of  the  blood  ;  but  it  is 
only  fair  to  Bennett  to  state  that,  in  discussing  the  nature  of  the 
blood  change  in  this,  his  first,  communication  on  the  subject,  he 
qualified  this  opinion  by  the  following  statement : — "  Unless  there- 
fore it  could  be  shown  that  inflammation  and  fever  were  like  pro- 
cesses, we  must  conclude  that  the  alteration  of  the  blood  in  this  case 


140  DISEASES   OF   THE   BLOOD. 

was  independent  of  inflammation  properly  so  called"  (no  italics  in  the 
original). 

Very  shortly  (a  few  weeks)  afterwards,*  Virchow  published  a 
case,  which  had  been  independently  observed  by  him  prior  to  the 
publication  of  Bennett's  first  communication  on  the  subject,  and 
pointed  out  that  the  white  corpuscles  found  in  the  blood  were  white 
blood  corpuscles  and  not  pus  cells  ;  he  consequently  termed  the 
condition  "  weisses  Blut "  or  leukaemia. 

A  keen  controversy  was  waged  for  some  time  between  these 
two  celebrated  men  and  their  supporters,  both  as  to  the  question 
of  priority  of  discovery  and  as  to  the  correctness  of  their  respective 
interpretations  of  the  blood  condition.  Bennett  used  to  give  a 
most  entertaining  lecture  on  the  subject.  Every  one  who  attended 
his  lectures  on  Physiology  or  Clinical  Medicine  will  remember 
what  a  treat  it  was.  Hughes  Bennett  was  a  man  of  acute  intellect 
and  of  great  dramatic  power.  He  was,  however,  an  advocate  rather 
than  a  judge;  and  I  need  hardly  say  that  in  describing  his  contro- 
versy with  Virchow  and  Virchow's  supporters  he  left  us  students 
completely  under  the  belief  that  his  (Bennett's)  opponents  had  not 
a  leg  to  stand  upon.  I  now  take  a  somewhat  different  view  of  the 
position.  It  must,  I  think,  be  allowed  that  while  Bennett  was  the 
first  to  observe  and  publish  an  accurate  and  detailed  description  of 
the  pathological  appearances  and  blood  changes  in  leucocythsemia,f 
Virchow  was  the  first  to  give  an  intelligent  explanation  of  the 
peculiar  alteration  in  the  blood  which  is  the  essential  characteristic 
of  the  disease.  Further,  it  is  important  to  note  that  very  shortly 
after  his  first  publication  on  the  subject  the  great  German  patho- 
logist recognised  the  fact  that,  in  some  cases  of  leucocythsemia, 
the  increase  of  the  white  corpuscles  is  due  to  an  increase  of  the 
large  white  cells  of  the  blood,  while,  in  others,  it  is  due  to  an 
increase  of  the  small  white  cells  ;  and  that  in  some  cases  the  spleen 
is  enlarged,  while  in  other  cases  the  lymphatic  glands  are  enlarged. 
Basing  the  distinction  upon  these  points  of  difference,  Virchow 
consequently  divided  cases  of  leukaemia,  as  he  termed  the  condi- 
tion, into  two  varieties — the  splenic  and  the  lymphatic  forms  of 
leukaemia  respectively. 


*  Bennett's  first  case  was  observed  on  19th  March  1845,  and  published  on 
1st  October  1845.  Virchow's  first  case  was  observed  on  1st  August  1845,  and 
published  in  the  second  week  of  November  1845. 

t  One  or  two  individual  cases  had  been  reported,  before  Bennett  and 
Virchow  described  the  condition,  without  their  peculiar  nature  and  character 
being  recognised. 


LEUCOCYTH/EMIA.  14T 

In  the  years  185 1  and  1852,  Hughes  Bennett  published  a  series 
of  papers  and  a  systematic  work  on  the  subject,  in  which  he 
advanced  the  view  that  the  lymphatic  and  other  ductless  glands 
secrete  the  blood,  and  proposed  that  the  name  leucocythaemia  or 
white-celled  blood  (from  \evKos  =  white,  Kin-os  =  cell,  and  atjxa  =  blood), 
which  has  since  been  generally  adopted  as  a  more  appropriate 
term  than  leukaemia  or  white  blood  (from  XevKos  =  white,  and  at/xa  — 
blood),  should  be  applied  to  the  disease. 

Varieties. —  In  most  cases  of  leucocythaemia  the  spleen  is 
markedly  enlarged  ;  and  until  comparatively  recently  it  was  sup- 
posed that  the  spleen  was  the  primary  and  fundamental  seat  of  the 
lesion  ;  hence  the  term  splenic  leucocythaemia  was  for  a  long  time 
applied  to  the  disease.  But  recent  observations  have  shown  that  in 
some  of  the  cases  in  which  the  spleen  is  markedly  enlarged  and  the 
blood  is  loaded  with  white  corpuscles  the  marrow  of  the  bones  is 
not  only  diseased  but  is  in  all  probability  the  primary  seat  of  the 
lesion.  To  these  cases  the  term  spleno-medullary  or  lieno-mediillary 
leucocythaemia  is  now  generally  applied. 

In  other  cases  of  leucocythaemia  in  which  the  spleen  is  also 
generally,  but  not  necessarily,  enlarged,  though  the  enlargement  is 
not  usually  so  great  as  in  the  spleno-medullary  form,  the  lymphatic 
glands  are  enlarged  ;  to  this  variety  the  term  lymphatic  leucocy- 
thaemia is  usually  applied. 

But  this  use  of  the  terms  splenic  and  lymphatic  leucocythaemia 
(founded  upon  the  presence  or  absence  of  enlargement  of  the 
spleen  and  lymphatic  glands)  is  not  strictly  accurate  for  the 
following  reasons  : — 

(a)  In  both  the  spleno-medullary  and  the  lymphatic  forms  of 
leucocythaemia  the  spleen  may  be  greatly  enlarged  ;  (b)  in  some 
cases  of  spleno-medullary  leucocythaemia,  more  especially  in  the 
later  stages  of  the  disease,  the  lymphatic  glands  are  enlarged  ;  and 
(c)  in  some  (apparently  quite  exceptional)  cases  of  lymphatic 
leucocythaemia,  the  spleen  is  enlarged  while  the  lymphatic  glands 
are  not  enlarged. 

Hence,  as  Dr  Robert  Muir  has  recently  pointed  out,  the  lymphatic 
form  of  leucocythaemia  is  not  synonymous  with  a  leucocythaemia 
in  which  the  lymphatic  glands  are  enlarged.  In  other  words,  the 
distinction  between  the  spleno-medullary  and  lymphatic  varieties 
of  leucocythaemia  cannot  be  based  merely  upon  the  presence,  in  the 
one  case,  of  an  enlarged  spleen,  and,  in  the  other,  of  enlarged  lym- 
phatic glands,  but  should  be  based  upon  the  exact  microscopical 
characters  of  the  white  corpuscles  to  which  the  leucocythaemic 
condition  is  due. 


142  DISEASES   OF   THE   BLOOD. 

In  spleno-medullary  leucocythaemia,  a  great  variety  of  different 
white  corpuscles  are  usually  present  in  the  blood  ;  but,  in  most 
(typical)  cases,  the  increase  of  the  white  corpuscles  is  in  great  part 
due  to  the  presence  of  large  nucleated  white  corpuscles,  which  do  not 
stain  with  eosin  and  which  appear  to  be  identical  with  certain  cells  of 
the  marrow  of  the  bones  (hence  the  term  myelocytes  which  has  been 
given  to  them) ;  in  some  cases  of  spleno-medullary  leucocythaemia, 
the  eosinophile  cells,  which  are  normally  present  in  the  blood  in 
small  proportion  (h  to  4  per  cent.),  are  also  greatly  increased 
in  number  ;  but  this  is  by  no  means  always  the  case,  or  perhaps 
it  would  be  more  correct  to  say  that  while  the  total  number  of 
eosinophile  cells  in  the  blood  is  (usually)  increased,  the  percentage 
of  eosinophile  cells  to  the  total  number  of  white  corpuscles  is  usually 
less  than  the  normal. 

In  the  lymphatic  form  of  leucocythaemia,  the  increase  of  the 
white  corpuscles  of  the  blood  is  almost  entirely  due  to  an  increase 
of  the  uninucleated  white  corpuscles,  and,  in  most  cases,  of  the 
small  uninucleated  corpuscles  (lymphocytes),  which  are  normally 
present  in  the  blood  in  considerable  proportion  (25  to  30  per  cent). 

A  few  rare  cases  of  leucocythaemia  have  also  been  described  in 
which  neither  the  spleen  nor  the  lymphatic  glands  were  affected, 
but  in  which  the  lesion  seemed  to  be  situated  in  the  medulla  of  the 
bones  ;  to  these  cases  the  term  medullary  leucocythaemia  has  been 
applied.  There  is,  however,  considerable  doubt  as  to  the  exact 
nature,  indeed  as  to  the  actual  occurrence  of  cases  of  this  kind, 
though  for  a  priori  reasons  I  am  disposed  to  think  that  cases  of 
pure  medullary  leucocythaemia  probably  occur. 

It  has  also  been  suggested  that  a  pure  splenic  leucocythaemia 
may  occur  ;  but  this  is  still  more  doubtful. 

In  some  cases  of  leucocythaemia,  the  marrow  of  the  bones,  the 
spleen  and  the  lymphatic  glands  are  all  involved  ;  in  other  cases,  all 
the  lymphoid  tissues  throughout  the  body  are  affected  (enlarged), 
and  lymphoid  deposits  may  even  be  developed  in  organs  and  tissues 
in  which  they  are  not  normally  present  or  apparent. 

We  may  say,  then:  —  (1)  That  leucocythaemia  is  (usually)  a 
chronic  and  slowly  progressive  condition  which  is  characterised 
clinically  by  : — (a)  An  enormous  increase  of  the  white  blood  cor- 
puscles ;  (b)  more  or  less,  and  in  some  cases  marked,  diminution 
of  the  red  blood  corpuscles  and  haemoglobin  ;  and  (c)  in  some 
cases,  by  enlargement  of  the  spleen  ;  in  others  by  enlargement  of 
the  lymphatic  glands  ;  and  in  others  by  a  combination  of  these 
conditions  (enlargement  of  the  spleen  and  lymphatic  glands).  (2) 
That  so   far  as  our  present   knowledge  enables  us  to  judge,  the 


LEUCOCYTH/EMIA.  1 43 

spleno-medullary  and  lymphatic  forms  of  leucocythaemia  appear 
to  be  distinct  conditions  or  varieties.  (3)  That  other  varieties  of 
leucocythaemia  (a  purely  medullary  form,  for  example),  may  per- 
haps occur. 

Further,  it  should  be  added  that  the  spleno-medullary  is  far 
more  common  than  the  lymphatic  variety  of  the  disease. 

The  exact  relationship  of  the  lymphatic  form  of  leucocythaemia 
to  Hodgkin's  disease  has  not  yet  been  satisfactorily  determined. 
To  the  naked  eye,  the  glandular  lesions  in  the  lymphatic  form  of 
leucocythaemia  and  in  Hodgkin's  disease  are  very  similar,  and  some 
observers  state  that  they  are  identical  in  character  ;  but  so  far  as 
my  observation  enables  me  to  judge,  the  enormous  glandular 
enlargements  which  are  met  with  in  some  cases  of  Hodgkin's 
disease  are  never  developed  in  cases  of  lymphatic  leucocythaemia. 
Further,  Dr  Robert  Muir  tells  me  that  his  observations  show  that 
the  lymphatic  glands,  when  affected  in  leucocythaemia,  are  simply 
crowded  with  leucocytes,  similar  in  character  to  those  which  are 
present  in  excess  in  the  blood,  and  the  enlarged  lymphatic  glands 
•do  not  present  the  proliferative  changes  in  the  stroma,  leading  to 
indurations,  which  are  common  in  Hodgkin's  disease. 

When  I  come  to  describe  Hodgkin's  disease  I  will  point  out 
that  the  peculiar  form  of  glandular  enlargement  (a  hard  painless 
enlargement  of  many  different  groups  of  lymphatic  glands),  which 
is  its  chief  clinical  characteristic,  may  undoubtedly  be  due  to  more 
than  one  pathological  process,  for  example  to  Hodgkin's  disease 
and  to  tubercle,  and  that  in  some  cases  it  is  difficult  or  impossible 
to  differentiate  these  conditions  during  life. 

Some  writers  advocate  the  view  that  lymphatic  leucocythaemia 
is  a  combination  of  Hodgkin's  disease  and  leucocythaemia.  But 
to  my  mind  this  view  is  not  altogether  satisfactory.  It  merely 
expresses  the  fact  that,  in  some  cases  of  disease  in  which  the 
lymphatic  glands  are  enlarged  and  in  which  that  enlargement 
presents  the  same  clinical  characters  as  the  glandular  enlarge- 
ment characteristic  of  Hodgkin's  disease,  the  spleen  is  also 
enlarged  and  the  blood  contains  a  large  excess  of  white  cor- 
puscles. It  does  not  afford  any  satisfactory  explanation  of  the 
fact  that  in  many  (most)  typical  cases  of  Hodgkin's  disease  the 
white  corpuscles  are  not  increased,  or  at  all  events  not  markedly 
increased  ;  and  it  takes  no  account  of  the  exact  character  of  the 
white  blood  corpuscles  which  are  present.  In  some  cases  of 
Hodgkin's  disease  in  which  the  white  corpuscles  are  in  excess — and 
this  seems  chiefly  to  occur  in  the  later  stages  of  the  disease — the 
condition  appears  to  be  a  leucocytosis  and  not  a  lymphatic  leuco- 


144  DISEASES   OF   THE   BLOOD. 

cythaemia.  Further,  as  has  been  already  stated,  I  very  much 
doubt  whether  the  glandular  enlargement  is  identical  in  the  two 
conditions. 

Etiology. 

In  this  country,  leucocythaemia  is  a  very  rare  disease.  In  14,777 
consecutive  cases  of  medical  disease  which  I  have  analysed,  there 
were  only  five  cases  of  leucocythaemia.* 

Age  and  Sex. — Leucocythaemia  is  much  more  common  (pro- 
bably at  least  three  times  more  common)  in  men  than  in  women. 
In  the  great  majority  of  cases,  the  disease  is  developed  during  active 
adult  life,  between  the  ages  of  25  and  50,  though  cases  also  occur 
in  childhood  ;  the  disease  is  very  rare  in  old  age.  The  spleno- 
medullary  form  is  more  common  in  adults,  the  lymphatic  form 
appears  to  be  more  common  in  children. 

Locality,  race,  etc.— The  disease  occurs  in  all  parts  of  the  world 
and  affects  all  races,  though,  according  to  Eichhorst,  it  is  particularly 
apt  to  affect  Jews  ;  it  appears  to  be  more  frequent  in  the  lower  than 
the  upper  ranks  of  society. 

Influence  of  malaria,  traumatic  injury,  etc. — In  a  considerable 
proportion  (according  to  Gowers  20  per  cent.)  of  cases,  the  disease 
occurs  in  persons  who  have  previously  suffered  from  malaria  ;  but, 
so  far  as  I  know,  it  has  not  been  shown  that  the  disease  is  more 
prevalent  in  tropical  and  malarial  districts  than  in  temperate 
climates.  The  disease  would,  however,  appear  to  be  much  more 
common  in  certain  parts  of  America  than  it  is  in  this  country. 
Thus,  Stengel  states  that  he  has  seen  15  cases  during  the  past 
four  years  in  Philadelphia,  and  at  least  12  during  the  past  year 
in  the  hospital  service  and  private  practice  of  himself  and  col- 
leagues.! Whether  the  greater  frequency  of  malaria  accounts  for 
the  frequency  with  which  leucocythaemia  seems  to  occur  in  America 
or  not  I  cannot  say.  Further,  the  nature  of  the  connection  which 
seems  to  prevail  between  certain  cases  of  leucocythaemia  and  malaria 
is  entirely  unknown. 

In  some  cases,  traumatic  injuries  (blows  over  the  spleen,  etc.) 
appear  to  have  been  the  exciting  cause  of  the  condition.  In  other 
cases,  the  onset  of  the  disease  has  been  preceded  by  mental  anxiety 
or  overwork.  In  one  of  my  cases  the  disease  seemed  to  develop 
after  an  attack  of  influenza.  It  is  probable  that  these  conditions 
merely  act  as  contributory  or  predisposing  causes  ;  it  can  hardly 
be  supposed  that  they  are  the  actual  causes  of  the  disease. 


*  I  have,  of  course,  seen  and  had  under  my  care  several  other  cases, 
t  "Twentieth  Century  Practice  of  Medicine,"  Vol.  vii.,  p.  401. 


LEUCOCYTHAEMIA.  145 

Since  in  women  the  disease  appears  as  a  rule  to  occur  at  a  some- 
what later  age  than  in  men,  it  has  been  supposed  that,  in  some 
instances  at  least,  its  development  in  women  is  related  to  the 
occurrence  of  the  menopause.  Pregnancy,  lactation  and  uterine  or 
ovarian  derangements  appear  in  some  cases  to  have  an  influence  as 
predisposing  or  exciting  causes  of  the  disease;  though  this  relation- 
ship may  perhaps,  as  Muir  has  suggested,  be  merely  accidental. 

In  rare  cases,  the  disease  appears  to  be  hereditary  or  to  affect 
more  than  one  member  of  the  same  family. 

The  ultimate  cause  ;  possibly  an  irritant  in  the  blood  ;  ?  micro- 
organisms.— The  true  (the  fundamental)  cause  of  leucocythaemia 
is  as  yet  unknown.  It  has  been  suggested  (and  some  of  the  clinical 
and  pathological  characters  of  the  disease  seem  to  favour  this  view) 
that  the  disease  is  due  to  some  form  of  intoxication — to  the  intro- 
duction into  the  body  of  an  irritant  which  has  a  special  and  specific 
influence  upon  the  organs  in  which  the  white  blood  corpuscles  are 
formed  (the  marrow  of  the  bones,  the  lymphatic  glands  and  the 
spleen)  ;  and  in  some  cases  micro-organisms  have  actually  been 
detected  in  the  blood.  But  in  other  cases  in  which  micro-organisms 
have  been  carefully  searched  for,  none  have  been  found.  Further 
information  is,  therefore,  required  before  any  definite  statement  can 
be  made  on  this  point.  It  is  possible  that  future  observation  may 
show  that  in  some  cases  leucocythaemia  is  due  to  micro-organisms, 
while  in  others  it  is  not.  The  same  line  of  argument  which  has 
been  advanced  with  regard  to  the  role  which  micro-organisms  may 
possibly  play  in  the  production  of  pernicious  anaemia  may  perhaps 
be  applied  to  leucocythaemia. 

With  regard  to  the  exact  nature  and  ultimate  causation  of  the 
disease,  Muir  states  : — "  In  the  absence  of  knowledge  regarding  the 
agent  producing  the  excessive  proliferation  of  leucocytes,  we  cannot 
definitely  assign  the  place  of  leucocythaemia  in  the  category  of 
disease.  On  the  whole,  it  presents  most  points  of  analogy  to  the 
growth  of  tumours,  the  analogy  being  especially  striking  in  the 
lymphatic  variety  ;  but,  on  the  other  hand,  it  is  not  absurd  to 
suppose  that  it  may  yet  prove  to  be  due  to  a  microparasite."  * 

The  primary  seat  of  the  lesion. — Two  views  have  been  held  as 
to  the  primary  seat  of  the  disease,  viz.,  (1)  That  the  increase  of 
leucocytes  takes  place  in  the  blood  itself,  and  that  the  lesions  in 
the  bone-marrow,  spleen,  lymphatic  glands,  etc.,  are  secondary :  (2) 
That  the  increase  of  the  leucocytes  is  due  to  an  abnormal  or  patho- 

*  Article  on  Leucocythaemia  in  Clifford  Allbutt's  "  System  of  Medicine," 
Vol.  v.,  p.  652. 

K 


146  DISEASES   OF   THE   BLOOD. 

logical  over-production  of  white  cells  in  the  organs  (bone-marrow, 
spleen,  lymphatic  glands)  in  which  the  white  corpuscles  of  the  blood 
are  normally  formed. 

The  latter  view  is  the  one  which  is  now  generally  held  and  is  in 
all  probability  correct;  though  in  some  cases  evidence  has  been 
found  that  in  leucocythaemia  the  leucocytes  may  go  on  increasing 
in  the  blood  itself  or  in  the  tissues  and  organs  in  which  they  are 
extra vasated  or  deposited  from  the  blood,  just  as  they  seem  to  do 
in  normal  blood  to  a  certain  extent.  The  presence  of  leucocytes 
containing  nuclei  in  an  active  state  of  division  seems  to  show  that 
this  may  occur. 

Some  authorities  have  supposed  that  the  increase  of  the  leuco- 
cytes in  leucocythaemia  is  due  to  defective  destruction,  an  abnormal 
accumulation  of  leucocytes  in  the  blood,  so  to  speak  ;  but  the  evi- 
dence seems  strongly  to  support  the  contrary  opinion,  viz.,  that 
the  increase  is  the  result  of  over-production  in  the  blood-forming 
organs.  Probably,  as  has  been  already  suggested,  this  over-produc- 
tion may  be  due  to  more  than  one  cause,  and,  in  different  cases  and  in 
different  forms  of  leucocythaemia,  may  have  its  chief  seat  in  different 
parts  of  the  blood-forming  organs  and  tissues  (marrow  of  the  bones, 
spleen,  lymphatic  glands,  etc.). 

I  have  already  stated  that  cases  of  leucocythaemia  (in  both  of 
which  the  spleen  may  be  enlarged)  may  be  divided  into  two  main 
varieties,  which  have  been  termed  (a)  the  spleno-medullary  and  {b) 
the  lymphatic  types  or  forms  of  leucocythsemia  respectively.  The 
different  characters  of  the  blood  (the  white  corpuscles)  would  seem 
to  show  that  these  two  varieties  of  leucocythaemia  are  separate  and 
distinct  diseases.  It  has  been  suggested  that  the  two  forms  are 
occasionally  met  with  in  combination,  but  so  far  as  I  know  this  has 
not  as  yet  been  actually  demonstrated.  If  the  two  forms  do  occur 
in  combination,  it  must  of  course  be  admitted  that  the  distinction 
between  the  spleno-medullary  and  lymphatic  forms  of  leucocythaemia 
is  not  always  so  definite  and  distinct  as  the  statement  which  has  just 
been  made  would  imply. 

In  the  great  majority  of  cases  of  leucocythaemia  in  which  the 
spleen  is  enlarged,  the  marrow  of  the  bones  is  found  diseased  after 
death  ;  and  in  this,  the  spleno-medullary  form  as  it  is  now  usually 
termed,  the  lesion  of  the  marrow  of  the  bones  is  regarded  by  most 
modern  authorities  as  the  primary  and  fundamental  lesion.  This 
opinion  is  based  upon  the  microscopical  characters  of  the  white 
corpuscles  which  are  present  in  this  form  of  leucocythaemia,  and 
particularly  upon  the  presence  in  the  blood  of  large  uninucleated 
corpuscles  which  do  not  stain  with  cosin  and  which  appear  to  be 


LEUCOCYTHAEMIA.  147 

identical  with  certain  cells  which  are  normally  present  in  the  bone- 
marrow  (myelocytes).  This  opinion  seems  to  be  corroborated  by 
the  fact  that  in  this  variety  of  leucocythsemia  nucleated  red 
blood  corpuscles  are  present  in  the  blood,  often  in  considerable 
numbers.  Further,  cases  of  leucocythaemia  have,  as  I  have  already 
stated,  been  described  in  which  the  spleen  and  lymphatic  glands 
were  normal,  and  in  which  the  only  lesion  appeared  to  be  a  lesion 
of  the  marrow  of  the  bone.  Again,  it  is  probable,  I  think,  that  the 
diminution  of  the  red  blood  corpuscles,  which  constitutes  one  of  the 
clinical  characteristics  of  spleno-medullary  anaemia,  is  due  to  the 
changes  in  the  bone-marrow — in  other  words,  is  the  result  of  defec- 
tive production,  rather  than  excessive  destruction,  of  red  blood 
corpuscles.  So  far  as  I  know,  there  is  nothing  to  show  that  in 
the  spleno-medullary  form  of  leucocythaemia  there  is  an  excessive 
destruction  of  red  blood  corpuscles. 

And  here  I  may  state  that  the  great  majority  of  physiologists 
now  admit  that  the  red  blood  corpuscles  are  formed  from  nucleated 
red  cells,  and  that  they  are,  under  normal  circumstances,  produced 
in  the  marrow  of  the  bones.  The  view  which  was  at  one  time 
held,  that  the  red  blood  corpuscles  are  produced  from  the  white 
blood  cells  and  that  the  diminution  in  red  blood  corpuscles  in 
splenic  leukaemia  is  the  result  of  defective  formation  of  red  blood 
•cells  from  white  corpuscles,  is  rapidly  losing  ground  and  may  in 
fact  be  said  to  be  abandoned  by  almost  all  authorities. 

Morbid  Anatomy. 

On  examining  the  bodies  of  patients  who  have  died  from 
leucocythaemia,  the  remarkable  condition  of  the  blood  and  the  great 
enlargement  of  the  spleen  are  the  two  most  constant  and  striking 
naked-eye  features. 

The  conditions  of  the  blood  and  blood  vessels. — The  con- 
dition of  the  blood  is  very  remarkable.  In  many  typical  cases,  the 
blood  vessels  are  over-distended  with  brick-red-coloured  or  choco- 
late-brown-coloured blood,  or  contain  pale  purulent-looking  clots. 
The  clots  which  are  present  in  the  heart  usually  have  a  peculiar 
yellowish-green  colour.  In  some  cases  the  cardiac  cavities  seem 
to  be  filled  with  pus.  The  purulent  appearance  is  due  to  the  fact 
that  the  white  blood  corpuscles  are  apt  to  separate  from  the  red 
corpuscles  and  collect  together,  forming  a  greenish-yellow,  creamy- 
looking  fluid  which  closely  resembles  pus. 

The  veins  and  smaller  blood  vessels  in  the  different  organs  may 
be  over-distended  with  white  corpuscles. 


I48  DISEASES   OF   THE    BLOOD. 

In  one  case  which  I  examined  some  years  ago,  and  recorded  in 
the  "British  Medical  Journal,"  18S6,  Vol.  ii.,  p.  1098,  the  veins  on 
the  surface  of  the  brain  were  enormously  distended  with  brick- 
red  and  chocolate-coloured  blood  ;  the  brain  looked  as  if  it  were 
covered  with  large  red  worms.  The  appearance  was  a  very  remark- 
able one. 

Haemorrhagic  extravasations. — A  tendency  to  haemorrhage, 
both  into  the  internal  organs  and  from  the  mucous  surfaces  of  the 
body,  is  one  of  the  most  striking  features  of  the  disease  when  it  is 
severe  and  advanced.  In  the  case  to  which  I  have  just  referred, 
numerous  haemorrhages,  most  of  them  microscopic  but  some  of  large 
size,  were  scattered  throughout  the  brain  substance.  The  small 
vessels  in  the  interior  of  the  brain  were  all  engorged  and  over- 
distended  with  white  blood  corpuscles.  Many  of  them  were  dilated, 
presenting  here  and  there  a  varicose  or  aneurismal  appearance. 

Exactly  the  same  condition  may  be  seen  in  other  organs.  The 
vessels  of  the  liver  and  kidney,  for  example,  may  be  engorged  with 
white  blood  corpuscles,  and  the  lymphatic  sheaths  and  tissues 
round  the  distended  vessels  may  also  contain  large  numbers  of 
white  blood  cells.  In  the  case  to  which  I  have  just  referred,  the 
vessels  of  the  spinal  cord  as  well  as  the  vessels  of  the  brain  and 
all  the  organs  of  the  body  were  enormously  distended  with  white 
blood  cells. 

Localised  collections  of  white  corpuscles  and  lymphoid  deposits,, 
which  in  many  cases  appear  to  be  the  result  of  the  multiplication 
in  situ  of  white  blood  cells  which  have  escaped  from  the  blood 
vessels,  may  be  seen  in  the  different  tissues  and  organs.  These 
infiltrations  of  leucocytes  in  the  different  tissues  and  organs,  giving 
rise  to  localised  lymphatic  deposits  and  enlargements,  appear  to  be 
much  more  common  and  prominent  in  the  lymphatic  than  in  the 
spleno-medullary  variety  of  the  disease. 

The  distended  condition  of  the  veins  and  the  difficulty  with 
which  the  white  blood  corpuscles  circulate  through  the  distended 
vessels  is  one  cause  of  the  thromboses,  which  are  apt  to  occur  in  the 
course  of  the  disease. 

The  microscopical  characters  of  the  blood  will  be  more  appro- 
priately considered  in  connection  with  the  clinical  history. 

Spleen. — The  spleen  is  in  some  cases  so  much  enlarged  that  it 
occupies  a. large  part  of  the  abdominal  cavity;  it  not  unfrequently 
weighs  six  or  seven  pounds,  and  one  case  has  been  recorded  in  which 
it  reached  the  enormous  weight  of  eighteen  pounds.  The  capsule  is 
very  often  thickened  ;  in  some  cases,  dense  adhesions  bind  the  en- 
larged spleen  to  the   surrounding  organs  and  to  the  adjacent  wall 


leucocytHjEmia.  149 

of  the  abdomen.  The  organ  is  usually,  and  especially  in  long- 
standing cases,  firmer  and  harder  than  normal.  The  enlargement 
appears  to  the  naked  eye  to  be  a  simple  hypertrophy,  with  an  in- 
creased production  of  fibrous  tissue.  In  the  more  rapidly  developed 
cases,  the  spleen  is  usually  less  enlarged  and  softer  in  consistence 
than  in  the  more  common  (chronic)  cases. 

On  section,  the  spleen  usually  has  a  uniform,  brownish-yellow, 
brownish -grey,  or  reddish -brown  colour.  In  most  cases,  the 
Malpighian  corpuscles  cannot  be  differentiated  by  the  naked  eye 
from  the  splenic  pulp.  In  other  cases,  the  Malpighian  bodies  stand 
out  as  pale  points  in  the  midst  of  the  darker  splenic  tissue.  In 
some  cases,  hsemorrhagic  extravasations,  in  others,  infarctions, 
usually  wedge-shaped  and  in  various  stages  of  decoloration,  are 
present. 

In  some  cases  of  (lymphatic)  leucocythsemia,  nodules  of  a  whitish 
colour  are  scattered  here  and  there  throughout  the  spleen.  In  these 
cases,  the  enlargement  of  the  spleen  is  not  usually  great. 

On  microscopical  examination,  the  splenic  tissue  is  seen  to  be 
infiltrated  and  the  splenic  sinuses  crowded  with  white  corpuscles  ; 
in  some,  more  especially  long-standing,  cases,  the  fibrous  tissue  is 
greatly  increased  in  amount.  The  white  cells  are  for  the  most 
part  ordinary  leucocytes,  but  myelocytes  and  nucleated  red  blood 
corpuscles  are  present  in  the  spleno-medullary  variety  of  the 
disease.  Dr  Robert  Muir  informs  me  that  his  observations  seem 
to  show  that  the  character  of  the  leucocytes  in  the  splenic  pulp 
correspond  more  or  less  closely  to  those  in  the  blood — in  the 
spleno-medullary  form  they  consist  chiefly  of  myelocytes,  the 
eosinophile  cells  being  often  also  in  excess  ;  in  the  lymphatic  form, 
they  consist  chiefly  of  lymphocytes.  Pigment  granules  or  crystals 
of  hsematin,  the  results  of  previous  haemorrhages,  may  be  seen  in 
different  parts  of  the  section.  Small  colourless  octahedral  crystals, 
which  were  first  described  by  the  late  Professor  Charcot,  are  some- 
times found  in  the  blood  and  splenic  tissue  after  death. 

Lymphatic  glands  and  other  lymphoid  tissues. — In  the  great 
majority  of  cases  of  lymphatic  leucocythaemia,  the  lymphatic  glands 
are  more  or  less,  and  in  some  cases  considerably,  enlarged.  In  the 
spleno-medullary  form,  the  lymphatic  glands  may  also  be  enlarged, 
but  this  is  not  usually  the  case.  The  enlarged  glands  may  be  firm 
or  soft.  On  section,  they  have  generally  a  yellowish-pink  or 
reddish  colour. 

On  microscopical  examination,  the  gland  tissue  is  found  to  be 
crowded  with  white  corpuscles,  usually  of  small  (lymphocytes), 
but  in  some  cases  (spleno-medullary  form)  of  larger  size. 


150  DISEASES   OF   THE   BLOOD. 

The  tonsils,  thymus  gland,  the  Peyers  patches  and  solitary  glands 
in  the  intestine  are  in  some  cases  affected  ;  and  lymphoid  deposits 
are  sometimes  also  present  in  the  stomach,  lungs,  the  serous  mem- 
branes, retina  and  even  in  the  skin.  The  lymphoid  deposits  in  the 
intestine  are  in  some  cases  ulcerated.  These  lesions  are  much 
more  common  in  the  lymphatic  variety  of  the  disease. 

Bone-marrow. — Changes  in  the  marrow  of  the  bones  are  con- 
stantly present  in  the  spleno-medullary  variety,  but  are  usually  less 
marked  and  characteristic  in  the  lymphatic  form.  Neumann  was 
the  first  to  direct  attention  to  the  changes  in  the  marrow  of  the 
bones  which  are  now  regarded  by  most  authorities  as  the  primary 
lesion  in  the  spleno-medullary  form  of  the  disease. 

On  naked-eye  examination,  the  marrow  is  seen  to  be  of  a 
yellowish-grey  or  reddish  colour,  to  which  Neumann  applied  the 
terms  pyoid  and  lymphoid  respectively  ;  the  latter  is  much  the  more 
frequent. 

On  microscopical  examination,  it  is  found  that  the  fat  cells,  which 
are  normally  present  in  the  marrow  in  great  abundance,  have  for 
the  most  part  disappeared.  In  the  spleno-medullary  form,  the 
marrow  tissue  contains  an  excessive  number  of  large  uninuclcated 
marrow  cells,  eosinophile  cells  and  nucleated  red  blood  corpuscles, 
and  lymphoid  corpuscles.  In  the  lymphatic  variety,  the  marrow 
tissue  is  infiltrated  with  uninucleated  white  corpuscles  similar  to 
those  which  are  present  in  excess  in  the  blood.  The  trabecular 
and  even  the  shaft  of  the  bone  may  be  atrophied. 

Heart. — The  muscular  tissue  is  usually  flabby,  pale  and  more 
or  less  fatty,  the  cardiac  cavities  being  in  some  cases  considerably 
dilated.  Petechial  haemorrhages  may  be  present  in  the  pericardial 
or  endocardial  surfaces. 

On  microscopical  examination,  the  minute  blood  vessels  in  the 
cardiac  wall  may  be  greatly  distended  with  leucocytes,  and  minute 
collections  (extravasations)  of  white  blood  corpuscles  may  be 
present  here  and  there  in  the  sub-pericardial  tissue  or  between 
the  muscular  fibres. 

Liver. — The  liver  is  usually  considerably  enlarged,  its  surface 
smooth  and  its  consistency  usually  firm.  On  section,  it  generally 
presents  a  more  or  less  uniform  dull-red  colour  ;  in  some  cases,  the 
surface  of  the  section  is  markedly  mottled,  the  peripheral  parts  of 
the  lobules  being  pale  owing  to  the  leucocytic  infiltration  along  the 
portal  tracts.  Small  whitish-yellow  deposits,  which  to  the  naked 
eye  resemble  tubercles,  but  which  consist  of  lymphoid  tissue,  may 
be  scattered  here  and  there  in  the  midst  of  the  liver  tissue. 

On  microscopic  examination,  the  minwte  blood  vessels  are  usually 


LEUCOCYTHAEMIA.  I  5  I 

found  to  be  markedly  distended  with  leucocytes,  and  large  numbers 
of  leucocytes  may  be  infiltrated  and  scattered  in  the  midst  of  the 
hepatic  tissue.  In  some  cases,  nucleated  red  blood  corpuscles  and 
evidences  of  active  nuclear  division  {mitosis)  in  the  white  corpuscles 
have  been  seen  in  the  liver — changes  which  have  been  thought  to 
indicate  a  return  to  the  fcetal  blood-forming  function  of  the  organ. 
In  many  cases,  the  leucocytes  are  collected  in  small  masses  which 
are  evidently  the  starting  points  of  the  lymphoid  nodules  previously 
described. 

Kidneys. — The  kidneys  are  usually  more  or  less  enlarged  ;  the 
surface  is  generally  smooth,  the  capsule  unadherent,  and  the  section 
paler  than  normal.  In  some  cases,  lymphoid  nodules  can  be  seen 
with  the  naked  eye  on  the  surface  of  the  organ. 

On  microscopical  examination,  the  minute  vessels  may  be  greatly 
distended  with  white  corpuscles,  and  enormous  numbers  of  leu- 
cocytes may  be  infiltrated  and  extravasated  through  the  renal 
tissues.  The  renal  epithelium  is  usually  more  or  less  fatty  or  in  a 
condition  of  cloudy  swelling. 

In  the  description  which  has  just  been  given  of  the  morbid 
appearances  met  with  in  the  bodies  of  patients  who  have  died  from 
leucocythaemia,  I  have  not  thought  it  necessary  to  give  a  separate 
description  of  the  morbid  appearances  in  the  two  varieties  of 
leucocythaemia — the  spleno-medullary  and  the  lymphatic  forms  ; 
though,  as  has  already  been  stated,  these  two  varieties  seem,  so 
far  as  our  present  knowledge  enables  us  to  judge,  to  be  distinct 
diseases.  As  I  have  previously  stated,  some  authorities  suppose 
that  the  two  varieties  may  occur  in  combination  ;  while  this  is 
theoretically  possible,  further  observation  seems  to  be  required 
before  this  view  can  be  definitely  accepted. 

Clinical  History. 

Mode  of  onset  and  Course. — The  onset  of  leucocythaemia  is 
usually  slow  and  insidious,  and  the  course  chronic.  In  rare  cases 
(which  are  almost  invariably  cases  of  the  lymphatic  variety)  the 
onset  is  acute  and  the  course  rapid.  In  many  of  the  chronic  cases, 
paroxysmal  exacerbations  of  the  symptoms  occur  from  time  to 
time. 

Symptoms  and  complaints. —  In  the  great  majority  of  cases, 
the  patient  slowly  and  gradually  begins  to  lose  strength  and  colour, 
and  complains  of  a  feeling  of  fulness,  weight  and  heaviness  in  the 
abdomen,  due  to  the  presence  of  the  enlarged  spleen.  Intercurrent 
attacks  of  pain  in  the  region  of  the  spleen  are  of  frequent  occur- 


152  DISEASES   OF   THE    BLOOD. 

rence.  In  some  cases,  the  pain  is  probably  due  to  acute  congestion 
and  stretching  of  the  capsule;  in  others,  to  perisplenitis  or  localised 
peritonitis.  As  the  disease  advances,  the  patient  becomes  breath- 
less on  exertion,  suffers  from  palpitation  and  the  other  symptoms 
characteristic  of  anaemia.  In  some  cases,  intercurrent  attacks  of 
fever  every  now  and  again  occur.  Priapism  has  been  noted  in  a 
considerable  proportion  of  cases  ;  in  some  cases,  it  is  an  early 
symptom.  It  is  probably  the  result  of  over-distension  or  of 
thrombosis  of  the  corpora  cavernosa  with  leucocythaemic  blood. 

Tenderness  of  the  bones  (sternum,  tibiae,  etc.)  is  occasionally 
complained  of,  and,  when  it  does  occur,  is  highly  suggestive  of  im- 
plication of  the  bone-marrow. 

General  appearance. — On  examination,  the  abdomen  is  found 
to  be  distended,  often  enormously  so.  In  the  majority  of  cases,  the 
distension  is  chiefly  due  to  the  enlarged  spleen,  partly  to  the 
enlarged  liver  ;  but  in  a  few  cases  it  is  in  some  degree  the  result  of 
associated  ascites. 

In  the  vast  majority  of  cases,  the  complexion  (skin  and  mucous 
membranes)  is  pale,  but  this  is  not  invariably  so  ;  for  cases  are 
occasionally  met  with  in  which  the  skin  of  the  face  and  the  mucous 
membranes  of  the  lips  are  well,  indeed  too  deeply,  coloured.  I 
happen  to  possess  an  admirable  water-colour  drawing  by  Mr  John 
Williamson  of  a  case  in  point. 

The  patient  was  a  woman,  aged  33  ;  the  spleen  was  enormously 
enlarged  ;  the  face  (cheeks,  nose,  chin)  and  lips  were  deeply  injected 
and  mottled  ;  the  red  corpuscles  numbered  3,120,000  and  the  white 
corpuscles  310,000  per  cubic  millimetre  ;  the  case  was  one  of  spleno- 
medullary  leucocythaemia. 

To  this  exceptional  condition  the  term  "  lencocythcemic  plethora" 
has  been  applied.  It  apparently  is  the  result  of  an  over-distended 
condition  of  the  peripheral  vessels  of  the  face  and  lips.  It  is  not 
unreasonable  to  suppose  that  the  vessels  of  the  face  and  mucous 
membrane  of  the  lips  may  in  some  cases  be  chronically  over- 
distended  with  chocolate-coloured  blood  just  as  the  vessels  on  the 
surface  of  the  brain  may  be.  But  this  condition  (leucocythaemic 
plethora)  is  quite  exceptional.  In  the  great  majority  of  cases  of 
leucocythaemia  the  face  is  pale  and  the  buccal  and  conjunctival 
mucous  membranes  more  or  less  anaemic.  In  some  cases  in  which 
the  face  is  pale  the  lips  are  well  coloured.  I  happen  to  have  a  case 
of  this  kind  in  the  hospital  at  the  present  time. 

General  state  of  nutrition. — One  important  point  in  which 
leucocythaemia  differs  from  chlorosis  and  pernicious  anaemia  is  the 
fact  that,  when    the  disease  is  thoroughly  established,  the  patients 


LEUCOCYTH^EMIA.  153 

are  usually  more  or  less  emaciated,  often  markedly  so.  In  many 
cases,  the  enlarged  abdomen  forms  a  striking  contrast  to  the 
emaciated  condition  of  the  upper  and  lower  extremities  and  of  the 
face.  In  this  respect  the  clinical  picture  resembles  to  some  extent 
that  of  cirrhosis  of  the  liver. 

Dropsy. — CEdema  of  the  feet  and  ankles  is  common  in  the 
advanced  stages,  especially  in  those  cases  in  which  the  anaemia 
is  marked.  The  face  is  sometimes  puffy.  Localised  swellings  in 
the  face,  neck,  etc.,  may  be  the  result  of  the  pressure  of  enlarged 
glands  upon  the  vessels. 

The  condition  of  the  spleen. — On  examining  the  abdomen,  the 
enlarged,  hard  and  weighty  spleen  is  easily  recognised.  The  normal 
shape  of  the  organ  is  usually  well  preserved  ;  the  anterior  border 
is  usually  sharply  defined,  and  in  it  one  or  more  notches  can  usually 
be  felt — points  of  distinction  between  the  enlarged  spleen  and  the 
enlarged  left  kidney.  Further,  the  splenic  tumour  moves  with 
respiration,  is  not  overlapped  by  the  colon  (though  this  cannot 
always  be  demonstrated),  and  does  not  usually  distend  the  left  loin 
so  fully  (i.e.,  does  not  extend  so  far  back  towards  the  spinal  column 
in  the  lumbar  region)  as  a  tumour  of  the  left  kidney  does. 

In  some  cases,  there  is  tenderness  on  pressure  over  the  enlarged 
spleen.  In  others,  a  friction  fremitus  may  be  felt  with  the  hand,  or 
a  friction  sound  may  be  heard  when  the  stethoscope  is  placed  over 
the  splenic  tumour.  Pulsations  can,  it  is  said,  be  occasionally  felt 
in  the  enlarged  spleen  ;  in  one  of  my  cases  a  loud  blowing  murmur 
was  audible  with  the  stethoscope  ;  but  these  conditions  (pulsation 
and  murmur)  are  quite  exceptional. 

The  enlarged  spleen  may  vary  considerably  in  size  from  time  to 
time  ;  these  variations  are  chiefly  seen  in  the  earlier  stages  of  the 
disease  (i.e.,  before  the  development  of  fibrous  overgrowth). 

The  condition  of  the  liver. — As  I  have  already  said,  the  liver 
is  usually  considerably  enlarged.  Free  fluid  is  sometimes  present 
in  the  peritoneal  cavity  ;  but  a  marked  degree  of  ascites  appears 
to  be  quite  exceptional  ;  in  none  of  my  cases  was  ascites  present. 
The  abdominal  dropsy  is  usually  supposed  to  be  due  to  the  pressure 
of  the  enlarged  spleen  or  of  enlarged  lymphatic  glands  upon  the 
portal  vessels. 

The  condition  of  the  blood. — A  drop  of  blood  obtained  by 
puncturing  the  finger  may  be  well  coloured,  or  paler  or  more  opaque 
(turbid)  than  normal ;  in  some  cases  it  may  look  like  a  mixture  of 
blood  and  pus. 

On  microscopic  examination,  the  white  blood  corpuscles  are  found 
to  be  enormously  increased  in  number,  while  the  red  blood  corpuscles 


154  DISEASES   OE   THE   BLOOD. 

and  the  haemoglobin  are  usually  diminished,  sometimes  in  a  marked 
degree. 

In  health,  the  number  of  white  blood  corpuscles  varies  consider- 
ably j  the  average  number  being  usually  about  8,000  per  cubic  milli- 
metre. In  cases  of  leucocythaemia,  the  white  cells  may  number 
200000,  300,000,  400,000,  or  even  more,  per  cubic  millimetre. 

The  proportion  of  white  to  red  corpuscles  (which  should  not, 
however,  be  taken  as  the  standard)  is  greatly  altered.  The  white 
corpuscles  are  enormously  increased,  while  the  red  corpuscles  are 
diminished  in  number  though  not  (usually)  in  a  very  marked  degree. 
In  leucocythaemia  it  is  not  uncommon  to  have  one  white  to  every 
five  or  six  red  corpuscles,  and  cases  have  been  recorded  in  which 
the  white  corpuscles  have  actually,  it  is  said,  been  as  numerous  as 
the  red. 

In  thirty  cases  of  leucocythaemia  observed  by  Cabot,  the  average 
number  of  white  corpuscles  was  438,000  per  cubic  millimetre. 

In  leucocythaemia,  as  in  health,  the  number  of  white  blood  cor- 
puscles may  vary  considerably  from  time  to  time.  A  remarkable 
case  has  been  recorded  by  Strieker  in  which,  at  one  period  of  the 
case,  the  white  bipod  corpuscles  were  more  numerous  than  the  red, 
but,  at  a  subsequent  period,  there  was  only  one  white  blood  cor- 
puscle to  every  150  red  cells.  Dr  Muir  makes  the  following  state- 
ment, which  is  of  great  diagnostic  importance,  that  even  in  those 
(rare)  cases  of  (spleno-medullary)  leucocythaemia  in  which  the 
excess  of  white  corpuscles  disappears,  temporarily  or  before  death,, 
the  abnormal  form  of  cells  (large  uninucleated  non-amceboid  leuco- 
cytes, nucleated  red  corpuscles,  etc.)  which  are  characteristic  of  the 
disease  remain  in  the  blood.*  I  can  confirm  Dr  Muir's  observa- 
tions on  this  point,  for  in  a  case  which  is  at  present  under  my  care 
the  white  corpuscles  have  fallen,  as  the  result  of  treatment,  from 
210,000  per  cubic  millimetre  to  1,600  per  cubic  millimetre,  and  yet 
amongst  the  very  scanty  number  of  white  corpuscles  which  are 
present  a  considerable  proportion  of  myelocytes  are  still  to  be 
found. 

The  character  of  the  white  blood  corpuscles  differs  in  different 
cases  of  leucocythaemia  in  which  the  spleen  is  enlarged.  As  has 
been  already  stated,  Virchow  originally  recognised  these  differences 
and  described  two  varieties  of  the  disease,  the  splenic  and  lymphatic 
varieties  respectively  ;  and  for  many  years  past  I  have  been  in  the 
habit  of  teaching  that  in  cases  of  splenic  anaemia  (or  spleno- 
medullary  anaemia  as   it  is  now  termed)  the  white  corpuscles  are 

*  Clifford  Allbutt's  "System  of  Medicine,"  Vol.  v.,  p.  640. 


leucocythaemia.  155 

large  and  coarsely  granulated  ;  whereas  in  cases  of  lymphatic  leuco- 
cythaemia  the  white  corpuscles  are  of  small  size  and  not  coarsely 
granulated.  Modern  methods  of  staining,  for  the  introduction  of 
which  we  are  chiefly  indebted  to  Ehrlich,  have  shown  that  these 
differences  are  well  founded  and  of  the  greatest  diagnostic 
importance. 

The  microscopical  characters  of  the  blood  in  the  spleno- 
medullary  form  of  leucocythaemia. — -In  the  spleno-medullary  form 
of  leucocythaemia,  several  different  forms  of  white  corpuscles  are 
present.  Some  of  these  forms  exist  normally  in  the  blood,  others 
do  not.  The  most  characteristic  is  a  large  uninucleated  cell,  which 
does  not  generally  contain  eosinophile  granules  and  which,  unlike 
the  normal  white  blood  corpuscles,  does  not  exhibit  active  amceboid 
movements  on  the  warm  stage.  In  freshly  drawn  blood,  these  cells 
are  usually  about  twice  the  size  of  the  normal  red  blood  corpuscles 
(about  16  fi.  in  diameter),  though  in  dried  films  they  may,  in  con- 
sequence of  flattening  out  during  the  process  of  preparation,  appear 
to  be  considerably  larger.  Their  exact  nature  has  given  rise  to  a 
good  deal  of  debate.  It  has  been  supposed  that  they  are  degene- 
rated white  corpuscles,  but  most  observers  are  now  agreed  that  they 
are  identical  with  certain  cells  which  are  normally  present  in  the 
marrow  of  the  bones.  They  have  therefore  been  termed  myelocytes. 
Though  occasionally  present  in  small  number  in  other  conditions 
(chiefly  in  severe  forms  of  anaemia,  whether  primary  or  secondary, 
and  in  wasting  diseases),  myelocytes  are,  so  far  as  is  known,  never 
present  in  the  blood,  in  large  numbers,  except  in  leucocythaemia  ; 
and  since  in  the  spleno-medullary  form  of  the  disease  they  usually 
constitute  a  large  proportion  of  the  white  corpuscles — 30  per  cent, 
or  even  more  —  they  are  of  the  highest  diagnostic  significance. 
They  are  sometimes  met  with  in  small  numbers  in  the  lymphatic 
form  of  leucocythaemia. 

In  18  cases  of  spleno-medullary  leucocythaemia  observed  by 
Cabot,  the  average  percentage  of  myelocytes  to  the  total  number 
of  white  corpuscles  in  the  blood  was  37.7  per  cent.,  rising  in  one  case 
as  high  as  60  per  cent,  and  never  lower  than  20  per  cent.  He 
states  : — ■ 

"  Taking-  the  average  total  number  of  leucocytes  as  438,000  per  cubic  milli- 
metre, the  absolute  number  of  myelocytes  would  be  over  162,000  per  cubic 
millimetre.  So  far  as  I  am  aware  the  highest  count  of  myelocytes  in  any  other 
disease  is  that  mentioned  on  page  128  in  a  case  of  pernicious  anaemia,  namely, 
1,150  per  cubic  millimetre.  The  contrast  is  sufficiently  striking.  I  wish  to 
insist  upon  this  point,  namely,  that  the  blood  of  splenic-myelogenous  leukaemia 
is  absolutely  peculiar  and  characteristic,  and  could  not  be  confused  with  that  of 
any  other  disease.     Certain  writers  of  late  years  have  concluded   that  because 


156  DISEASES   OF   THE   BLOOD. 

myelocytes  do  occur  in  a  great  variety  of  diseases  as  well  as  in  leukaemia,  there- 
fore there  is  nothing  peculiar  about  the  blood  of  the  latter  affection.  It  would 
be  as  logical  to  say  that  because  albumin  and  casts  occur  occasionally  in  the 
urine  of  persons  practically  well,  therefore  there  is  nothing  characteristic  about 
the  urine  of  acute  nephritis. 

"  Between  the  largest  number  of  myelocytes  ever  recorded  in  any  disease 
other  than  leukaemia,  and  the  smallest  number  ever  found  in  the  latter  disease, 
there  is  as  great  a  difference  as  there  is  between  the  minute  traces  of  sugar  to 
be  found  in  normal  urine  and  the  marked  glycosuria  of  diabetes  mellitus."  * 

Cases  of  spleno-medullary  leucocythaemia  are,  however,  occa- 
sionally met  with  in  which  the  myelocytes,  either  as  the  result  of 
treatment  or  of  some  other  cause,  become  very  few  in  number.  I 
have  at  the  present  time  a  case  of  this  description  under  observa- 
tion ;  and  it  is  interesting  to  note  that  in  it  the  coarsely  grained 
eosinophile  cells  are  very  few,  and  nucleated  red-blood  corpuscles 
are  very  scanty.  The  details  of  this  somewhat  exceptional  case  are 
recorded  below  (see  page  171). 

In  some  cases  of  spleno-medullary  leucocythaemia,  the  eosino- 
phile ceils  (which  are  normally  present  in  the  blood  in  small  pro- 
portion— only  \  to  4  per  cent,  of  the  total  leucocytes)  are  also  greatly 
increased  (to  20  per  cent,  or  more  of  the  total  leucocytes)  ;  but  this 
is  by  no  means  always  the  case  ;  and  of  late  years  much  less 
significance  has  been  attached  to  the  presence  of  these  (eosinophile) 
corpuscles,  as  a  characteristic  feature  of  leucocythaemia,  than  Ehrlich 
originally  claimed  for  them.  In  the  spleno-medullary  form  of 
leucocythaemia,  the  actual  number  of  the  eosinophile  cells  in  the 
blood  is  probably  always  greater  than  in  health,  but  they  are  not 
always  relatively  increased  in  proportion  to  the  other  forms  of 
white  corpuscles  ;  and  they  may  be  greatly  increased  in  other  con- 
ditions (certain  skin  diseases,  for  example). 

Some  of  the  eosinophile  cells  are  of  large  size  ;  Dr  Robert  Muir 
states  that  they  are  never  present  in  normal  blood,  and  hence  they 
are  of  considerable  diagnostic  importance. 

The  total  number  of  polymorpho-nuclear  leucocytes  is  also  in- 
creased, but  their  relative  proportion  to  the  total  number  of  leuco- 
cytes is  considerably  decreased.  In  the  18  cases  analysed  by  Cabot, 
the  average  proportion  of 'polymorpho-nuclear  cells  to  the  total 
number  of  white  corpuscles  was  49.2  per  cent,  instead  of  65  to  70 
per  cent,  as  in  health. 

The  total  number  of  lymphocytes  in  the  blood  is  also  increased 
in  some  cases,  but  their  relative  proportion  to  the  total  number  of 
white  corpuscles  is  markedly  diminished.     Dr  Muir  states  that  the 

*  "  Clinical  Examination  of  the  Blood,"  page  144. 


LEUCOCYTH^MIA.  157 

lymphocytes  are  not  increased.*  In  the  18  cases  observed  by 
Cabot,  the  average  was  7.6  per  cent,  instead  of  20  to  30  per  cent, 
(the  normal  average). 

In  the  spleno-medullary  form,  nucleated  red  blood  corpuscles  are 
usually  present  in  the  blood  and  generally  in  considerable  numbers 
— in  far  larger  numbers  than  in  any  other  condition.  They  are 
sometimes  of  large  size  (megaloblasts) ;  in  some  cases  their  nuclei 
are  seen  to  be  in  an  active  state  of  division. 

Further,  in  some  cases  there  is  distinct  evidence  that  some  of 
the  white  corpuscles,  more  especially  the  large  uninucleated  myelo- 
cytes, are  undergoing  active  division  {karyokinesis).  The  white 
corpuscles  containing  nuclei  in  an  active  state  of  division  {mitotic 
figures)  are  rarely  seen  in  normal  blood,  and  the  number  of  white 
corpuscles  in  leucocythaemia  which  show  this  change  is  always, 
relatively  to  the  total  number  of  white  corpuscles  which  are  present, 
very  small. 

The  microscopical  characters  of  the  blood  in  the  lymphatic 
form  of  leucocythaemia. — In  the  lymphatic  form  of  leucocythaemia 
(in  which  the  spleen  may  also  be  enormously  enlarged,  though  the 
enlargement  is  usually  much  less  than  in  cases  of  lymphatic  leuco- 
cythaemia, and  in  which,  as  Dr  Muir  has  shown,  the  lymphatic 
glands  are  not  necessarily,  though  they  are  in  the  great  majority  of 
cases,  enlarged)  the  increase  of  the  leucocytes  is  for  the  most  part 
due  to  an  enormous  increase  of  the  uninucleated  white  corpuscles, 
either  small  or  large,  but,  in  most  cases,  of  the  small  lymphocytes, 
which  normally  exist  in  the  blood  in  moderate  proportion  (20  to  25 
per  cent,  of  the  total  leucocytes).  It  has  indeed  been  stated  that 
the  increase  of  the  white  corpuscles  in  this  form* of  leucocythaemia 
is  entirely  due  to  an  increase  of  the  uninucleated  white  corpuscles  ; 
but  this  view  appears  to  be  a  mistake.  Dreschfeld  and  other 
writers  have  shown  that  in  this  form  of  leucocythaemia  other 
varieties  of  leucocytes  {eosinophile  cells  and  even  myelocytes)  may 
also  be  present ;  but  the  uninucleated  white  corpuscles  generally 
form  90  to  95  per  cent,  of  the  total  white  corpuscles  present. 

In  the  lymphatic  form  of  leucocythaemia,  nucleated  red  corpuscles 
are  rarely  present,  and  if  they  occur  are  only  present  in  very  small 
numbers. 

In  both  varieties  of  leucocythaemia,  the  red  blood  corpuscles  are 
usually  diminished  in  number,  sometimes  markedly  so.  In  well- 
marked  cases  of  the  disease  they  usually  number  from  2,500.000  to 
3,500,000  per  cubic  millimetre  ;  but  in  some  cases — and  this  state- 

*  Clifford  Allbutt's  "  System  of  Medicine,"  Vol.  v.,  p.  639. 


158  DISEASES    OF   THE    BLOOD. 

ment  more  particularly  applies  to  the  lymphatic  variety — the  reduc- 
tion is  even  more  marked  (1,500,000  or  even  less).  In  the  cases 
observed  by  Cabot,  the  average  number  of  red  corpuscles  per  cubic 
millimetre  was  3,000,000,  the  haemoglobin  being  diminished  in  the 
same  proportion — in  other  words,  the  individual  richness  of  the 
corpuscles  in  haemoglobin  (or  the  colour  index)  was  about  normal. 
In  some  cases,  the  colour-index  is,  at  certain  periods  of  the  case  at 
all  events,  above  the  normal  (see  Case,  page  171). 

In  some  cases  of  leucocythaemia,  the  red  corpuscles  are  mis- 
shapen {poikilocytosis)  ;  but  in  the  cases  which  have  come  under 
my  own  notice,  the  alterations  in  size  and  shape  have  not  been 
striking. 

As  has  been  already  stated,  nucleated  red  blood  cells,  many  of 
which  are  of  large  size  (megaloblasts),  may  be  present,  more  espe- 
cially in  the  spleno-medullary  form  of  the  disease. 

The  hiemoglobiu  is  usually  proportionately  diminished  with  the 
red  blood  corpuscles,  sometimes  more  so.  In  some  cases,  the 
haemoglobin  separates  more  readily  from  the  corpuscles  after  death 
than  in  normal  conditions  ;  and  Charcot's  crystals,  which  are  often 
found  on  post-mortem  examination  in  the  blood  of  leucocythaemia, 
have,  it  is  said,  been  seen  in  microscopic  preparations  of  blood 
freshly-drawn  during  life  from  the  spleen  or  finger-tip. 

The  blood-plates  arc  in  some  cases  markedly  increased  in 
number. 

The  leading  characters  of  the  blood  in  the  two  varieties  of 
leucocythaemia  are  summarised  by  Cabot  as  follows  : — 

"  (a.)   Splcnic-mvelogenous  Form. 

"  1.  Red  cells  about  3,000,000;  nucleated  forms  very  numerous. 

"  2.   White  cells  about  450,000,  of  which 

"  3.   Myelocytes  form  about  30  per  cent. 

"  (b.)  Lymphatic  Form. 

"  i.   Red  cells  about  3,000,000  or  lower  ;  nucleated  forms  rare. 

"  2.  White  cells  about  100,000  or  lower,  of  which 

"  3.  Lymphocytes  form  over  90  per  cent,  (the  large  or  the  small 
forms  may  predominate). 

"  4.   Myelocytes  and  eosinophilcs  very  scanty. 

"  V.)  Mixed  forms  occasionally  occur,  partaking  of  the  charac- 
teristics of  each  of  the  above." 

The  condition  of  the  skin. — In  some  cases  of  leucocythaemia, 
pigmented  patches  are  developed  in  the  skin.  In  one  of  my  cases, 
characteristic  patches  of  leucoderma  were  scattered  here  and  there 
over  the  surface  of  the  body.      In  another  case,  which  is  at  present 


LEUCOCYTH/EMIA.  1 59 

under  observation,  a  diffuse  erythematous  eruption  attended 
with  high  fever  and  followed  by  desquamation  of  the  skin  was 
developed  during  the  treatment  (see  infra).  Petechial  haemor- 
rhages in  the  skin  occasionally  occur  in  the  later  stages  of  the 
disease.  In  rare  cases,  lymphoid  nodules  are,  it  is  said,  developed 
in  the  skin  and  subcutaneous  tissue  and  can  be  seen  and  felt 
during  life.  In  some  cases  of  the  disease,  excessive  sweating  is 
present. 

In  a  considerable  proportion  of  cases,  and  as  has  already  been 
remarked  this  statement  chiefly  applies  to  the  lymphatic  variety  of 
the  disease,  the  superficial  lymphatic  glands  are  enlarged. 

The  condition  of  the  heart. — The  heart's  action  is  extremely 
feeble  ;  this  is  one  of  the  most  characteristic  features  of  the  disease. 
The  weakness  of  the  heart  of  course  largely  accounts  for  the  short- 
ness of  breath  on  exertion,  the  palpitation  and  the  tendency  to 
giddiness  and  faintness  which  are  in  many  cases  very  striking  and 
prominent  symptoms.  A  venous  hum  is  usually  present  in  the 
neck  and  a  systolic  murmur  in  the  pulmonary  area.  Mitral, 
tricuspid  and  systolic  murmurs  may  occur,  just  as  in  other  forms 
of  advanced  anaemia.  The  aortic  second  sound  is  in  some  cases 
accentuated  ;  and  in  this  respect  cases  of  leucocythaemia  may  differ 
from  pernicious  anaemia.  The  accentuation  of  the  aortic  second 
sound  is  probably  due  to  the  fact  that  the  leucocythaemic  blood 
has  greater  difficulty  than  normal  blood  in  circulating  through  the 
vessels  ;  the  white  blood  corpuscles  cling  to  the  sides  of  the  vessels, 
and  when  they  are  unduly  numerous  tend  to  choke  the  vessels  and 
to  produce  obstructions  (thromboses).  As  I  have  already  pointed 
out,  this  is  probably  one  of  the  reasons  why  haemorrhages  are  so 
common  in  this  disease.  In  the  advanced  stages  of  leucocythaemia, 
when  the  heart's  action  is  much  enfeebled,  the  accentuation  of  the 
second  aortic  sound  may,  of  course,  disappear.  The  pulse  is 
usually  increased  in  frequency,  often  considerably  so ;  and  is 
generally  soft  and  weak. 

Haemorrhages. — Haemorrhage  may  occur  from  the  external 
surfaces  ;  epistaxis  and  bleeding  from  the  gums  are  particularly 
common  ;  bleeding  from  the  stomach  and  bowel  are  by  no  means 
rare ;  occasionally  there  is  haematuria.  Haemorrhages  into  the 
retina  occur  in  a  certain  proportion  of  cases.  On  ophthalmoscopic 
examination,  the  fundus  is  usually  found  to  be  paler  than  normal ; 
the  retinal  veins  are  in  some  cases  enormously  distended  ;  localised 
deposits  of  white  blood  corpuscles  resembling  little  lymphoid 
growths  may  be  found  in  the  retina  after  death  and  are  occa- 
sionally seen  with  the  ophthalmoscope  during  life  ;  in  some  cases 


l6o  DISEASES   OF   THE"  BLOOD. 

the  optic  discs  are  swollen  and  inflamed  (papillitis).  To  these 
retinal  changes  the  term  leucocythcsmic  or  leukcumic  retinitis  has 
been  applied. 

The  condition  of  the  digestive  organs. — Symptoms  indicative 
of  derangement  of  the  digestive  functions  are  very  common.  As  a 
rule,  the  appetite  is  markedly  impaired.  Vomiting  is  of  frequent 
occurrence ;  in  some  cases  it  seems  to  be  due  to  the  irritation 
which  the  splenic  tumour  produces  on  the  stomach.  Constipation 
is  common,  and  obstruction  of  the  bowels  may  even  result,  from  the 
pressure  of  the  splenic  tumour  on  the  intestine.  Diarrhoea  is  apt 
to  occur,  and  in  many  cases  it  is  the  immediate  cause  of  death. 
Intercurrent  inflammations  of  the  peritoneum,  usually  localised  to 
the  region  of  the  spleen,  are  common. 

The  condition  of  the  urine. — The  urine  does  not  as  a  rule 
present  any  characteristic  naked-eye  alterations.  The  uric  acid  is 
increased  in  amount.  Albuminuria  and  hematuria  sometimes 
occur,  especially  in  the  later  stages  of  the  disease. 

The  condition  of  the  nervous  system.  —  Head  symptoms 
of  various  kinds  (haemorrhage,  vertigo,  fainting  fits,  somnolence, 
epileptiform  convulsions,  coma,  etc.)  are  apt  to  occur  during  the 
terminal  stages  of  the  disease.  Ollivier  and  Ranvier  have  described 
these  symptoms  in  great  detail.  They  sum  up  the  chief  points  in 
the  clinical  history  as  follows  : — ■ 

"  In  some  cases,  prodromal  symptoms  are  observed  ;  some  patients,  in  fact, 
complain  of  headache  for  a  longer  or  shorter  time  before  the  more  serious 
symptoms  develop.  Later,  swimming  sensations  in  the  head,  vertigo,  buzzing" 
in  the  ears,  sometimes  even  fainting  fits,  occur.  In  the  more  advanced  stages, 
hebetude,  soon  succeeded  by  somnolence,  is  observed.  Lastly,  the  patient  may 
pass  into  a  condition  of  coma,  which  may  be  more  or  less  prolonged,  but  which 
always  terminates  in  death. 

To  these  three  successive  periods  there  correspond  three  degrees  of  altera- 
tion in  the  brain.  The  first  degree  (headache,  vertigo,  and  the  other  phenomena 
which  have  been  mentioned  above)  is  explained  by  the  accumulation  of  white 
globules,  which  produce  slowing  of  the  circulation,  and  consequently  anaemia  of 
the  brain. 

A  more  advanced  accumulation  of  white  blood  corpuscles  increases  the  blood 
pressure  ;  the  capillaries  dilate,  the  cerebral  pulp  is  compressed,  in  consequence 
of  which  hebetude  and  somnolence  are  developed. 

In  the  third  degree,  haemorrhages  form  and  destroy  more  or  less  extensive 
portions  of  the  brain.  This  is  the  terminal  period,  during  which  coma  comes 
on,  and  death  ultimately  supervenes."  * 

To  sum  up,  cerebral  ancemia,  cerebral  compression,  and  cereb?'al 
hemorrhage  with  destruction  of  the  brain  tissue  arc,  according  to 

*  "Archives  de  Physiologie,"  1870,  p.  114. 


LEUCOCYTHAEMIA.  l6l 

these  authorities,  the  three  conditions  which  determine  the  cerebral 
symptoms  which  are  seen  in  patients  suffering  from  leucocythaemia. 

Convulsions  sometimes  precede  death.  In  some  cases  maniacal 
excitement  occurs. 

The  following  are  the  leading  pathological  details  of  a  case 
which  came  under  my  observation  while  I  was  pathologist  to  the 
Edinburgh  Royal  Infirmary.  In  it  the  head  symptoms  were  pro- 
minent and  the  vascular  lesions  in  the  brain  tissues  more  marked 
than  in  any  other  case  with  which  I  am  acquainted  : — 

Case  of  Leucocythaemia  with  very  extensive  vascular  lesions  in  the  brain. — 

The  patient,  a  shoemaker,  aged  40,  died  on  18th  May,  and  was  examined  post 
mortem  on  19th  May  1884.  He  had  suffered  for  some  time  from  the  usual 
symptoms  of  leucocythaemia,  but,  shortly  before  death,  had  complained  of  head- 
ache, and  had  become  maniacal. 

It  is  unnecessary  to  detail  the  exact  condition  of  every  organ.  Suffice  it  to 
say,  that  the  case  was,  in  every  way,  a  typical  one. 

The  blood  throughout  the  body  was  thick,  and  of  a  brick-red  colour,  exactly 
resembling  thick  anchovy  sauce.  Oft  microscopic  examination,  the  white  cor- 
puscles appeared  to  be  quite  as  numerous  as — indeed,  in  some  slides,  more 
numerous  than — the  red  blood  discs  ;  many  of  them  were  of  large  size,  and 
coarsely  granular. 

The  spleen  weighed  4  lbs.  8  ozs.  ;  the  liver,  10  lbs.  8  ozs.  ;  the  kidneys,  14 
and  13^  ozs.  respectively;  the  pericardium  was  in  a  condition  of  early  inflam- 
mation, and  there  were  numerous  pimctiform  ecchymoses  in  the  inflamed 
membrane,  under  the  endocardium,  in  the  pleura,  and  in  the  other  parts  of  the 
body  ;  the  bone-marrow  was  of  the  same  brick-red  colour  and  thick  consistence 
as  the  blood. 

The  brain  weighed  3  lbs.  1  oz.,  and  presented  a  very  remarkable  appearance. 
The  vessels,  on  the  surface,  were  enormously  distended  with  the  thick,  brick- 
red-coloured  blood,  and  looked  like  masses  of  huge  worms  ramifying  over  the 
surface  of  the  hemispheres.  In  vertical  sections  made  through  the  whole  brain, 
innumerable  extravasations  of  blood  were  found  in  the  brain-substance.  Some 
of  them  were  chocolate-coloured  and  of  large  size,  the  largest  being  fully  the 
size  of  a  hen's  egg  ;  others  were  just  visible  to  the  naked  eye.  On  microscopic 
examination,  the  whole  brain-tissue  (more  especially  the  white  matter)  was 
riddled  with  capillary  hsemorrhages.  The  blood  vessels  and  capillaries  through- 
out the  brain  were  enormously  dilated  and  distended  with  white  corpuscles, 
multitudes  of  which  had  escaped  into  the  lymphatic  sheaths  surrounding  the 
larger  vessels.  The  vessels  of  the  brain,  even  the  large  trunks,  were  almost 
entirely  destitute  of  red  blood  corpuscles.  Collections  of  red  discs  were  present 
in  the  large  (naked-eye)  extravasations,  but  the  large  hsemorrhages  were  for  the 
most  part,  and  the  small  (microscopic)  haemorrhages  were  (apparently)  entirely, 
composed  of  white  corpuscles. 

The  vessels  of  the  spinal  cord  were  dilated  in  the  same  way  as  the  vessels 
of  the  brain,  and  were  stuffed  with  white  blood  corpuscles. 

Several  haemorrhages  were  seen  with  the  naked  eye  in  the  retina;  the  optic 
papillae  were  much  swollen,  and,  on  microscopic  examination,  large  numbers  of 
white  blood  corpuscles  were  found  scattered  between  the  fibres  of  the  optic 
discs,  and  between  the  bundles  of  the  optic  nerves  behind  the  lamina  cribrosa. 

L 


1 62  DISEASES   OF   THE   BLOOD. 

A  careful  search  was  made  in  the  different  tissues  for  micro-organisms. 
No  organisms  were  found  in  the  brain.  The  superior  cervical  ganglion  of  the 
sympathetic  was  infiltrated  throughout  with  fine,  highly  refractile,  granular 
particles  of  uniform  size,  which  exactly  resembled  unstained  micrococci,  but 
which  did  not  take  on  any  of  the  ordinary  dyes  (gentian-violet,  methyl-violet). 
Before  examination,  the  sympathetic  ganglia  had  been  kept  for  a  considerable 
time  in  a  solution  of  gum,  sugar,  and  carbolic  acid  ;  whether  this  solution 
prevents  the  staining  of  micro-organisms  I  do  not  know,  but  I  have  on  several 
previous  occasions  suspected  that  such  was  the  case.  That  the  fine  granular 
particles,  which  looked  like  micrococci,  were  not  due  to  the  gum  and  sugar 
solution  I  feel  quite  certain  ;  for,  in  the  course  of  a  research  on  the  normal  and 
pathological  condition  of  the  sympathetic  ganglia  of  the  neck  and  abdomen, 
which  extended  over  three  years,  I  examined  a  very  large  number  of  ganglia 
which  had  been  kept  in  the  same  solution,  and  in  no  case,  except  in  this  one, 
was  this  peculiar  granular  micrococcus-like  appearance  seen.  Whether  any 
importance  is  to  be  attached  to  the  condition  I  am  unable  to  decide. 

The  condition  of  the  respiratory  system. — Pressure  symptoms 
of  various  kinds  may  also  of  course  be  developed  in  those  cases  in 
which  the  bronchial  or  mediastinal  glands  are  enlarged.  I  need  not 
refer  to  these  symptoms  in  detail ;  they  will  be  more  appropriately 
considered  in  connection  with  Hodgkin's  disease. 

Intercurrent  attacks  of  bronchitis,  oedema  of  the  lungs  and  a  low 
form  of  pneumonia  are  in  many  cases  the  immediate  cause  of  death. 

Acute  leucocythaemia. — Ebstein's  observations  *  show  that  in 
cases  of  acute  leucocythaemia  the  onset  is  sometimes  sudden,  the 
course  rapid  and  attended  with  considerable  fever  ;  haemorrhages 
from  the  gums  and  nose  sometimes  occur ;  purpuric  spots  may  be 
developed  in  the  skin,  and  haemorrhages  may  be  poured  out  into 
the  viscera  or  from  the  mucous  surfaces  ;  the  lymphatic  glands, 
spleen,  and  liver  enlarge  ;  in  some  cases  there  is  tenderness  over 
the  bones  ;  the  patient  becomes  profoundly  anaemic  and  asthenic  ; 
the  blood  contains  a  large  excess  of  leucocytes  (the  white  corpuscles 
in  some  of  the  cases  were  said  to  be  as  numerous  as  the  red);  finally, 
the  patient  may  sink  into  a  typhoid  state  ;  or  delirium,  coma,  or 
convulsions  may  be  developed. 

In  the  sixteen  cases  (all  verified  by  post  mortem)  which  Ebstein 
tabulated  and  analysed,  the  average  age  was  29  years,  the  youngest 
patient  being  5  years  and  the  oldest  59  years  ;  while  the  average 
duration  of  the  disease  was  5.8  weeks,  the  shortest  duration  being 
2I  and  the  longest  9  weeks. 

In  acute  leucocythaemia,  unhealthy  and  rapidly  formed  ulcerations 
in  the  mouth  are  of  frequent  occurrence,  and  are  highly  characteristic ; 
ulceration  in  other  parts  of  the  gastro-intestinal  tract  may  also  occur. 

*  "Deutsches  Arch.  f.  Klin.  Med.,"  Leipzig,  1889,  B.  xliv.,  p.  343. 


LEUCOCYTHAEMIA.  163 

The  clinical  features  and  course  of  this  acute  form  of  leucocy- 
thaemia  are  highly  suggestive  of  an  infective  process,  and  in  some 
cases  micro-organisms  (staphylococci  and  streptococci)  have  been 
found  in  the  blood  during  life,  and  in  the  organs  after  death.  In  a 
case  recorded  by  Dr  J.  S.  Fowler  a  bacillus  was  present  in  all  the 
blood  films  which  were  examined.* 

Diagnosis  and  Differential  Diagnosis. 

In  well-marked  cases  the  diagnosis  of  leucocythaemia  can 
usually  be  at  once  made  by  a  microscopical  examination  of  the 
blood.  Until  recently,  physicians  were  in  the  habit  of  regarding 
all  cases  of  leucocythaemia  in  which  the  spleen  was  enlarged  as 
cases  of  splenic  leucocythaemia,  and  of  considering  those  cases  of 
leucocythaemia  in  which  the  lymphatic  glands  were  enlarged  either 
as  cases  of  lymphatic  leucocythaemia  or  as  a  combination  of  leuco- 
cythaemia and  of  Hodgkin's  disease. 

But  recent  observations  as  to  the  exact  character  of  the  blood 
in  cases  of  leucocythaemia  show  that  the  diagnostic  problem  is  by 
no  means  so  simple  as  these  statements  would  imply. 

Further,  it  must  be  remembered  that  in  some  cases  of  leucocy- 
thaemia the  white  corpuscles  are  not  very  greatly  increased  in 
number ;  and  in  some  cases  in  which  they  are,  at  one  period  of  the 
case,  greatly  increased  in  number,  at  another  period  the  increase  is 
far  less  marked. 

If  the  patient  should  be  seen  at  a  period  at  which  the  total 
number  of  leucocytes  is  not  increased  or  is  only  slightly  increased 
(but  this  is,  of  course,  quite  exceptional)  the  diagnosis  can  only  be 
made  by  the  examination  of  stained  films — i.e.,  by  the  detection  in 
the  blood  of  myelocytes. 

It  is  hardly  necessary  to  state  that  leucocytosis  may  occur  in  a 
large  number  of  different  conditions  (inflammatory  and  cachectic 
conditions,  after  profuse  haemorrhage,  etc.)  ;  and  that  a  slight  degree 
of  leucocythaemia  (which  it  may  be  impossible  to  differentiate  from 
excessive  leucocytosis  by  the  mere  number  of  the  white  corpuscles) 
may,  as  I  have  already  stated,  be  the  result  of  disease  of  the  lym- 
phatic glands,  and  probably  of  disease  of  the  marrow  of  the  bones, 
the  spleen  being  unaffected. 

But  leucocytosis  is  usually  a  temporary  condition,  and  in  leuco- 
cytosis the  increase  of  the  white  corpuscles  is  always  due  to  an 
increase  of  the  polymorpho-nuclear  white  corpuscles — the  reverse  of 
the  condition  which  occurs  in  leucocythaemia  ;   for    although   the 

*  "Edinburgh  Hospital  Reports,"  Vol.  v.,  1898,  p.  13. 


1 64  DISEASES   OF   THE   BLOOD. 

total  number  of  polymorpho-nuclear  corpuscles  is  increased  in 
leucocythaemia,  the  relative  proportion  of  polymorpho-nuclear 
corpuscles  to  the  total  number  of  white  corpuscles  is  usually 
greatly  diminished  (49.2  per  cent,  instead  of  65  or  70  per  cent. — 
the  normal  proportion). 

Again,  enlargement  of  the  spleen  is  often  met  with  without 
leucocythaemia.  In  rare  cases  (cases  of  so-called  splenic  anaemia), 
as  I  have  previously  pointed  out  in  considering  the  diagnosis  of 
pernicious  anaemia,  the  spleen  is  enlarged  with  a  pronounced  con- 
dition of  anaemia,  but  without  any  increase  of  the  white  blood  cells. 
The  spleen  is  often  enlarged  as  the  result  of  chronic  malarial 
poisoning  ;  but  in  malarial  enlargement,  whether  acute  or  chronic, 
there  is  usually  a  diminution  rather  than  an  increase  of  the  white 
blood  corpuscles.  Considerable  enlargement  of  the  spleen  without 
leucocythaemia  may  also,  of  course,  be  the  result  of  portal  con- 
gestion, of  waxy  disease,  and  (rarely)  of  hydatid  cysts  and  other 
forms  of  new  growth. 

Further,  in  very  rare  and  exceptional  cases,  the  spleen  is  greatly 
enlarged,  the  blood  contains  an  enormous  excess  of  white  blood 
corpuscles,  and  rapid  recovery  takes  place  under  treatment.  It  is 
doubtful  whether  cases  of  this  kind  should  be  placed  in  the  same 
category  as  cases  of  ordinary  spleno-medullary  leucocythaemia  ; 
they  are  perhaps  due  to  a  different  cause  and  represent  a  distinct 
disease.  When  I  was  in  practice  in  North  Shields,  a  remarkable 
case  of  acute  leucocythaemia  came  under  my  notice.  The  notes  of 
the  clinical  history  are  briefly  as  follows  : — 

Case  of  Acute  Leucocythaemia :  Rapid  Recovery  under  Quinine.* — A  labourer, 
aged  35,  who  lived  in  a  damp  insanitary  house  on  the  banks  of  the  Tyne,  came 
under  my  care  in  the  year  1870.  He  had  been  ill  for  two  or  three  weeks  before 
I  saw  him.  The  disease  had  developed  rapidly;  it  was, in  short,  acute.  There 
was  some,  though  not  marked,  febrile  disturbance.  I  have  no  note  as  to  whether 
the  onset  was  attended  with  rigors.  The  patient  was  remarkably  pale  and 
cachectic-looking ;  his  colour  resembled  that  of  pernicious  anaemia  more  than 
anything  else.  The  spleen  was  greatly  enlarged ;  it  extended  down  almost  to 
the  pelvis,  filling  at  least  one  half  of  the  abdomen ;  the  lymphatic  glands  were 
not  enlarged ;  there  were  no  haemorrhages.  The  blood  contained  an  enormous 
excess  of  white  blood  cells.  Under  the  microscope,  the  white  blood  corpuscles 
seemed  quite  as  numerous  as  the  red.  At  that  time,  clinical  physicians  were 
not  in  the  habit  of  counting  the  blood,  and  I  cannot  say  what  the  exact  propor- 
tion of  white  to  red  blood  cells  was  ;  further,  we  were  not  then  able  to  differentiate 
the  different  forms  of  white  corpuscles  in  the  way  that  we  can  do  now  ;  I  can  say 
nothing  therefore  on  this  point,  but  the  appearance  of  the  blood  was  in  every 

*  This  case  is  not  included  in  the  five  cases  I  have  observed  in  my  series  of 
14,777  consecutive  cases  of  medical  diseases. 


LEUCOCYTH/EMIA.  1 65 

way  characteristic  and  typical  of  leucocythaemia.  I  was  well  acquainted  with 
the  disease,  splenic  leucocythaemia  or  leucocythasmia  as  it  was  then  simply  termed, 
from  Bennett's  teaching  and  from  cases  which  I  had  seen  in  the  Edinburgh 
Royal  Infirmary.  I  of  course  came  to  the  conclusion  that  the  patient  was  suffer- 
ing from  leucocythaemia  and  that  he  would  die  ;  but  taking  into  account  his 
insanitary  surroundings,  I  determined  to  try  the  effect  of  large  doses  of  quinine 
and  of  the  tincture  of  the  perchloride  of  iron.  Under  this  treatment,  the  symptoms 
rapidly  subsided  and  the  enlargement  of  the  spleen  and  the  excess  of  white 
corpuscles  disappeared  in  the  course  of  a  few  weeks'  time. 

I  was  at  the  time  disposed  to  think  that  in  this  case  the  condi- 
tion was  more  closely  allied  to  malaria  than  to  leucocythaemia ;  but 
I  now  know  that  in  ordinary  malarial  poisoning  a  marked  excess 
of  white  blood  corpuscles  such  as  was  present  in  this  case  is  not 
developed.  In  acute  malarial  poisoning,  there  is  rapid  destruction 
of  the  red  blood  cells,  and  diminution  of  the  leucocytes.* 

I  mention  the  case  in  proof  of  the  fact  that  the  presence  of  an 
enlarged  spleen  and  of  an  enormous  increase  in  the  white  blood 
corpuscles  is  not  necessarily  indicative  of  the  chronic  and  usually 
fatal  disease  to  which  the  term  splenic  leucocythaemia  used  to  be 
applied. 

A  considerable  number  of  cases  of  acute  lymphatic  leuco- 
cythaemia have  of  recent  years  been  described — Stengel  states  that 
the  total  number  is  now  more  than  40  f — but  they  appear  always 
to  have  been  fatal.  The  case  which  I  have  just  recorded  is,  so  far 
as  I  know,  unique,  inasmuch  as  it  ended  in  complete  recovery,  and 
that,  so  far  as  I  could  judge  from  the  mere  microscopical  characters 
of  the  unstained  blood,  the  white  corpuscles  were  of  large  size  and 
coarsely  granulated,  in  other  words  the  case  was  one  of  acute  spleno- 
medullary  (and  not  of  lymphatic)  leucocythaemia. 

Whether  cases  of  acute  leucocythaemia  are  due  to  the  same  cause 
(acting  in  a  more  intense  and  virulent  degree)  as  the  ordinary 
chronic  form  of  leucocythaemia  has  not  as  yet  been  determined. 

The  differential  diagnosis  of  spleno-medullary  leucocythsemia 

*  With  regard  to  the  condition  of  the  white  cells  in  malaria  Cabot  makes 
the  following  statement : — The  number  of  leucocytes  is  usually  subnormal,  but 
shows  a  slight  increase  at  the  beginning  of  the  paroxysm.  Following  this  increase 
there  is  a  rapid  decrease  continuing  throughout  the  paroxysm.  The  small 
number  of  leucocytes  is  to  be  seen  at  the  end  of  the  paroxysm  when  the  tem- 
perature is  subnormal.  From  this  time  it  shows  a  gradual  increase  until  the 
beginning  of  the  next  attack  (Billings). 

In  a  general  way  the  white  cells  follow  the  same  course  as  do  the  red. 

The  differential  count  shows  a  lymphocytosis  whenever  the  white  cells  are 
subnormal,  the  larger  forms  of  young  cells  being  especially  numerous,  while  the 
adult  cells  and  eosinophiles  are  scanty. 

+  "Twentieth  Century  Practice  of  Medicine,"  Vol.  vii.,  p.  436. 


166  DISEASES   OF   THE   BLOOD. 

and  of  lymphatic  leucocythaemia. — In  both,  the  blood  may  con- 
tain an  enormous  excess  of  white  blood  corpuscles  ;  and  in  both, 
the  spleen  and  lymphatic  glands  may  be  enlarged.  The  more 
important  points  of  distinction  are  as  follows  : — 

(i.)  The  enlargement  of  the  spleen  is  usually  much  greater  in 
spleno-medullary  leucocythaemia  than  in  lymphatic  leucocythaemia. 

(2.)  In  spleno-medullary  leucocythaemia  many  of  the  white 
corpuscles  are  large  and  coarsely  granulated  ;  the  increase  of  the 
white  blood  corpuscles  is  chiefly  due  to  an  increase  of  the  large 
nucleated  cells  which  do  not  stain  with  eosin,  which  do  not  exhibit 
active  amoeboid  movements  on  the  warm  stage,  and  which  appear 
to  be  identical  with  cells  which  are  normally  present  in  the  medulla 
of  the  bones  {myelocytes) ;  the  eosinophile  cells  may  be,  but  are  not 
necessarily,  greatly  increased  in  number.  In  the  spleno-medullary 
form  of  leucocythaemia,  nucleated  red  blood  corpuscles,  often  of 
large  size  (megaloblasts),  are  usually  present  in  considerable 
numbers. 

In  typical  cases  of  lymphatic  leucocythaemia,  the  increase  of 
the  leucocytes  is  almost  entirely  due  to  an  increase  of  the  uni- 
nucleated  white  corpuscles,  large  or  small,  but  especially  of  the  small 
lymphocytes  which  are  normally  present  in  the  blood  in  moderate 
proportion  ;  while  myelocytes  are  either  absent  or  present  only 
in  small  proportion,  and  nucleated  red  blood  corpuscles  are  not 
present,  or  are  only  present  in  very  small  numbers. 

In  short,  in  typical  and  uncomplicated  cases  of  spleno-medullary 
and  lymphatic  leucocythaemia  respectively,  the  microscopical  char- 
acters of  the  blood  are  totally  different,  and  enable  us  to  distin- 
guish the  two  conditions  with  absolute  certainty.  The  essential 
feature  of  the  blood  in  most  (typical)  cases  of  spleno-medullary 
leucocythaemia  is  the  great  excess  of  myelocytes  (which  constitute 
on  the  average  30  per  cent,  at  least  of  the  total  white  corpuscles 
which  are  present)  ;  while  the  essential  feature  of  the  blood  of  the 
lymphatic  variety  is  the  great  excess  of  the  uninucleated  white 
corpuscles  (which  constitute  on  the  average  at  least  90  per  cent,  of 
the  total  white  corpuscles  which  are  present). 

(3.)  In  many  (most)  cases  of  spleno-medullary  leucocythaemia 
the  lymphatic  glands  are  not  enlarged  ;  whereas  in  the  great 
majority  of  cases  of  lymphatic  leucocythaemia  the  lymphatic 
glands  are  enlarged.  But,  as  I  have  already  pointed  out,  the  dis- 
tinction between  the  two  varieties  of  leucocythaemia  should  not  be 
based  upon  the  condition  of  the  lymphatic  glands,  for  in  some 
cases  of  spleno-medullary  leucocythaemia  the  lymphatic  glands  are 
in  some  degree,  though  even  then  usually  only  slightly,  enlarged, 


LEUCOCYTH/EMIA.  1 67 

and  in  some  exceptional  cases  which  the  microscopical  examina- 
tion of  the  blood  shows  are  cases  of  lymphatic  leucocythaemia  the 
lymphatic  glands  are  (as  Dr  Robert  Muir  has  shown)  not  enlarged, 
while  the  spleen  is  greatly  enlarged. 

The  differential  diagnosis  of  leucocythaemia  and  Hodgkin's 
disease. — There  is  no  difficulty  in  distinguishing  typical  and  un- 
complicated cases  of  leucocythsemia  (whether  of  the  spleno- 
medullary  or  lymphatic  variety)  on  the  one  hand,  from  typical 
and  uncomplicated  cases  of  Hodgkin's  disease  on  the  other.  The 
distinction  is  at  once  made  by  a  microscopic  examination  of  the 
blood  ;  for  in  typical  and  uncomplicated  cases  of  Hodgkin's  disease 
the  white  blood  corpuscles  are  only  slightly  or  not  at  all  increased 
in  number. 

Further,  even  in  those  cases  of  Hodgkin's  disease  in  which  the 
white  corpuscles  are  increased,  there  is  usually  no  real  difficulty  in 
diagnosis.  The  distinguishing  point  is  the  different  character  of 
the  white  corpuscles  which  are  present,  viz.  : — (1)  In  the  spleno- 
medullary  form  of  leucocythaemia  the  large  number  of  myelocytes  ; 
(2)  in  the  lymphatic  form  of  leucocythaemia  the  large  number  of 
lymphocytes  ;  and  (3)  in  Hodgkin's  disease  with  leucocytosis,  the 
large  number  of  polymorpho-nuclear  leucocytes. 

From  this  statement  it  will  be  gathered  that  the  differential 
diagnosis  of  the  lymphatic  form  of  leucocythaemia  and  of  Hodgkin's 
disease  can,  in  most  cases,  be  made  by  a  microscopical  examination 
of  the  blood.  As  has  been  already  remarked,  the  etiological  and 
pathological  relationships  of  these  two  conditions  has  not  yet  been 
determined,  though  I  am  personally  disposed  to  think  that  they 
are  separate  and  distinct  conditions  and  not  merely  (as  some 
authorities  suppose)  different  stages  of  one  and  the  same  disease. 
Further,  I  doubt  the  correctness  of  the  view  which  supposes  that  in 
those  cases  of  Hodgkin's  disease  in  which  the  white  blood  cor- 
puscles are  in  excess,  the  condition  is  usually  due  to  a  combination 
of  Hodgkin's  disease  and  leucocythaemia,  as  many  authorities  seem 
to  suppose. 

The  differential  diagnosis  of  the  spleno-medullary  form  of 
leucocythsemia  and  of  the  myeloid  form  of  leucocythaemia. — I 
have  already  mentioned  that  some  cases  of  leucocythaemia  have 
been  recorded  in  which  the  spleen  was  not  enlarged,  and  in  which 
it  was  supposed  that  the  lesion  was  situated  in  the  marrow  of  the 
bones.  Cases  of  this  kind  are  exceedingly  rare.  They  are 
differentiated  from  cases  of  the  spleno-medullary  form  of  leucocy- 
thaemia by  the  fact  that  the  spleen  is  not  enlarged.  But  whether 
spleno-medullary    leucocythaemia    and    pure     medullary    leucocy- 


1 68  DISEASES   OF   THE   BLOOD. 

thaemia  (if  it  occurs)  are  separate  and  distinct  diseases,  or  merely, 
as  is  perhaps  more  probable,  varieties  of  the  same  disease,  has  not 
as  yet  been  definitely  determined.  Indeed,  Stengel  doubts  whether 
such  a  condition  as  pure  myeloid  leucocythaemia  occurs. 

The  differential  diagnosis  of  spleno-medullary  leucocy- 
thaemia and  of  splenic  ansemia. — Cases  of  splenic  anaemia  (pro- 
found anaemia  with  marked  enlargement  of  the  spleen,  in  which 
there  is  no  increase  of  the  white  blood  corpuscles)  are,  as  I  have 
already  stated,  rare  ;  no  case  has  come  under  my  own  notice.  The 
differential  diagnosis  can  usually  be  at  once  made  by  a  micro- 
scopical examination  of  the  blood  ;  but  it  must  be  remembered 
that  in  rare  cases  of  leucocythaemia  the  excess  of  white  corpuscles 
disappears  either  temporarily  as  the  result  of  treatment  or  before 
death.  Now  if  the  case  should  happen  to  be  seen  for  the  first  time, 
when  the  blood  is  free  from  an  excess  of  white  corpuscles,  the  true 
nature  of  the  case  might,  and  probably  would,  be  overlooked. 

The  differential  diagnosis  of  leucocythaemia  and  of  per- 
nicious anaemia. — This  presents  no  difficulty.  The  enlargement  of 
the  spleen  and  the  enormous  increase  in  the  white  blood  corpuscles 
are  quite  distinctive.  Some  authorities  have  assumed  that  there 
is  some  relationship  between  spleno-medullary  leucocythaemia  and 
pernicious  anaemia  ;  for  cases  have,  it  is  said,  been  met  with  in 
which  the  blood,  which  in  the  earlier  stages  presented  the  charac- 
ters of  leucocythaemia,  assumed  in  the  later  stages  the  characters, 
or  some  of  the  characters,  of  pernicious  anaemia,  the  excess  of  white 
blood  corpuscles  entirely  disappearing  and  the  blood  changes 
characteristic  of  pernicious  anaemia  being  ultimately  developed. 
That  some  such  alterations  in  the  blood  may  occur  is  perhaps  not 
to  be  wondered  at,  considering  that  in  both  diseases  (spleno- 
medullary  anaemia  and  pernicious  anaemia)  the  medulla  of  the 
bones  is  diseased  ;  but  that  leucocythaemia  may  be  transformed 
into  true  pernicious  anaemia  is  another  matter  and  requires,  I  think, 
further  demonstration  before  it  can  be  accepted  as  a  fact. 

Prognosis. 

This  is  most  unfavourable.  In  the  vast  majority  of  cases  of 
spleno-medullary  leucocythaemia,  the  disease  progresses  steadily 
downwards  and  ultimately  terminates  in  death,  though  intercurrent 
periods  of  improvement  not  unfrequently  occur.  A  fatal  issue  is, 
however,  not  invariable.  I  have  already  referred  to  a  case  of  acute 
splenic  leucocythaemia  in  which  complete  recovery  took  place ;  and 
in    the    ordinary  chronic  variety  of  the  disease   recovery  is  said 


LEUCOCYTH^MIA.  169 

occasionally,  though  very  rarely,  to  have  occurred  under  the 
influence  of  arsenic,  oxygen  inhalations,  and  other  measures  of 
treatment  to  which  I  will  presently  refer.  But  speaking  generally, 
in  the  present  position  of  our  therapeutic  knowledge,  the  treatment 
of  leucocythaemia  is  most  unsatisfactory. 

The  average  duration  of  the  disease  in  typical  and  well-marked 
cases  is  usually  said  to  be  from  one  to  three  years.  The  lymphatic 
variety  seems  in  most  cases  to  run  a  more  rapid  course  than  the 
spleno-medullary  form,  the  usual  average  being  from  four  weeks  to 
four  months. 

The  marked  tendency  to  haemorrhages  and  to  inflammatory 
lesions  is  a  very  important  point  in  connection  with  the  prognosis. 
In  those  cases  in  which  external  or  internal  bleeding  (epistaxis  in 
some  cases  excepted  *)  occurs,  and  in  which  vomiting  and  diarrhoea 
are  prominent  symptoms,  the  prognosis  is  most  unfavourable.  A 
rapid  diminution  of  the  red  corpuscles  in  spite  of  treatment  is  also 
unfavourable. 

The  occurrence  of  head  symptoms,  which  are  usually  only 
developed  shortly  before  death,  is  of  the  gravest  significance. 
Intercurrent  attacks  of  bronchitis,  oedema  of  the  lungs  and 
pneumonia  are  usually  fatal. 

Treatment. 

The  same  general  measures  which  have  been  previously  recom- 
mended in  cases  of  chlorosis  and  pernicious  anaemia  should  be 
adopted.  The  patient  should  be  kept  at  rest  in  bed  in  a  well- 
ventilated,  sunny  room.  Anything  which  is  likely  to  cause  cardiac 
strain  or  mental  excitement  should  be  avoided.  If  there  is  any 
suspicion  of  malaria  the  patient  should  be  removed  to  a  more 
salubrious  district. 

The  diet  must  be  carefully  regulated  ;  anything  which  is  likely 
to  produce  vomiting  and  diarrhoea  should  be  prohibited. 

Laxative  and  purgative  medicines  should  be  prescribed  with 
caution,  for  in  leucocythaemia  as  in  Addison's  disease  intractable 
diarrhoea  may  be  produced  by  a  comparatively  mild  purgative  and 
may  prove  fatal. 

Amongst  drug  remedies,  quinine  and  arsenic  are  by  far  the 
most  important,  more  especially  arsenic.     There  is  no  doubt  that 

*  The  mere  occurrence  of  epistaxis  is  not  necessarily  of  serious  significance  ; 
slight  bleedings  from  the  nose  may  occur  in  the  course  of  chronic  cases  without 
any  marked  deterioration  of  the  general  condition  ;  continued  bleeding  from  the 
nose  and  large  bleedings  are  unfavourable. 


170  DISEASES   OF   THE   BLOOD. 

in  some  cases  of  leucocythaemia  temporary  improvement  has  re- 
sulted from  the  continued  administration  of  gradually  increasing 
doses  of  arsenic.  In  those  cases  in  which  vomiting  is  prominent, 
the  arsenic  may  be  given  subcutaneously.  So  far  as  I  know,  it  has 
not  yet  been  definitely  determined  whether  arsenic  is  more  bene- 
ficial in  the  spleno-mcdullary  or  the  lymphatic  forms  of  the  disease, 
though  I  am  disposed  to  think  that  it  is  probably  more  beneficial 
in  the  lymphatic  variety.  Feeding  with  bone-marrow  also,  I  think, 
deserves  a  trial;  it  may  possibly  produce  benefit,  for  there  is  reason, 
as  I  have  previously  stated,  to  believe  that  in  spleno-medullary 
leucocythaemia  the  bone-marrow  is  always  diseased  and  is  in  fact 
the  primary  seat  of  the  lesion. 

Feeding  with  splenic  extract  or  splenic  tissue  has  also  been 
recommended.  I  have  not  had  the  opportunity  of  observing  the 
effects  in  any  case ;  so  far  as  I  know  it  is  useless  ;  and  this  is,  in 
fact,  only  what  one  would  on  a  priori  grounds  have  anticipated. 

Inhalations  of  oxygen  have  in  some  cases  been  attended  with 
marked  benefit,  and  in  any  future  cases  which  come  under  my 
notice  I  shall  certainly  give  this  plan  of  treatment  a  thorough  trial. 
In  other  cases  this  plan  of  treatment  has  proved  useless. 

In  those  cases  in  which  the  anaemia  is  marked,  iron  may  be 
tried.  Iodine  has  also  been  recommended.  Possibly  in  some 
cases  the  iodide  of  iron  may  be  beneficial ;  I  have  tried  it  and  I 
think  in  one  case  with  some  temporary  benefit. 

Local  measures  have  also  been  recommended  with  the  object  of 
producing  contraction  of  the  enlarged  spleen — painting  with  iodine, 
the  application  of  mercurial  ointment,  of  cold,  and  of  the  faradic 
current  over  the  enlarged  spleen.  In  some  cases  these  measures 
are  perhaps  attended  with  a  certain  measure  of  temporary  success. 
The  faradic  current  is  perhaps  the  most  effective  ;  under  its  use, 
the  enlarged  spleen  in  some  cases  undoubtedly  contracts,  but  the 
effect  so  far  as  I  know  is  merely  temporary  ;  I  doubt  whether  it 
produces  any  definite  or  distinct  influence  upon  the  course  of  the 
disease.  Several  years  ago,  I  tried  the  effect  of  galvano-puncture 
in  one  case  of  spleno-medullary  leucocythaemia  which  was  under 
my  care  in  the  Newcastle  Infirmary.  The  result  was  unsatisfactory  ; 
for  although  properly  insulated  needles,  such  as  are  used  in  the 
treatment  of  aneurism,  were  employed,  a  local  peritonitis  resulted. 
The  patient  died  shortly  afterwards  ;  but  it  is  only  right  to  say 
that  the  operation  was  practised  as  a  last  resource,  after  all  other 
means  had  been  employed,  and  when  the  patient  had  apparently 
only  a  few  days  to  live. 

Excision  of  the  spleen  has  also  been  practised,  but  the  results 


LEUCOCYTH/EMIA.  \"J\ 

of  the  operation  are  not  in  the  least  encouraging.  In  the  great 
majority  of  cases,  the  operation  has  only  been  attempted  in  the  last 
stages  of  the  disease  in  which  there  is  a  strong  tendency  to  death 
from  bleeding.  In  the  earlier  stages,  the  operation  is  perhaps 
attended  with  less  danger,  but  the  results  in  the  cases  which  have 
been  operated  upon  (according  to  Stengel  one  success  in  twenty 
operations)  prove,  in  my  opinion,  that  the  operation  is  unjustifiable. 
Further,  it  is  extremely  doubtful,  even  if  the  enlarged  spleen  could 
be  safely  removed,  whether  the  effect  would  be  satisfactory  and 
curative. 

In  the  present  position  of  our  knowledge,  the  systematic 
administration  of  arsenic  in  gradually  increasing  doses,  of  quinine, 
and  of  oxygen  inhalations  seem  to  be  the  measures  which  are  most 
likely  to  be  attended  with  benefit.  But  there  is,  I  think,  every  a 
priori  reason  to  believe  that  in  the  future,  when  our  knowledge  of 
the  exact  pathology  and  etiology  of  the  disease  is  more  advanced, 
some  more  efficient  and  satisfactory  means  of  treatment  will  be 
discovered. 

Quite  recently  Dr  William  Ewart  has  advised  the  administration 
of  carbonic  acid  gas  in  the  form  of  inhalations.*  The  details  of  a 
case  in  which  I  have  employed  the  remedy  are  given  below.  I  am 
disposed  to  think  that  the  rapid  disappearance  of  the  leucocytes 
from  the  blood,  which  took  place  in  that  case  during  the  treatment, 
was  probably  due  to  the  arsenic  or  to  the  oxygen,  or  to  both  of  these 
remedies,  rather  than  to  the  mercurial  inunctions  or  the  carbonic 
acid  inhalations.     The  notes  are  as  follows  : — 

A  Case  of  Spleno-Medullary  Leucocythaemia,  in  which,  under 
treatment,  the  white  corpuscles  rapidly  fell  from  210,000 
per  cubic  millimetre  to  1,600  per  cubic  millimetre. 

A.  H.,  aged  44,  schoolmaster,  married,  was  admitted  to  the  Edinburgh  Royal 
Infirmary  on  23rd  September  1898,  suffering  from  spleno- medullary 
leucocythaemia. 

Previous  history. — The  patient  enjoyed  excellent  health  until  a  year  ago. 
For  some  years  he  has  resided  in  a  healthy  seaside  place ;  he  has  never  suffered 
from  malaria.  Seven  years  ago,  he  had  an  attack  of  influenza  ;  for  some  years 
he  has  been  somewhat  liable  to  take  cold  and  has  had  several  sharp  attacks  of 
coryza. 

Last  Christmas,  he  had  an  attack  of  influenza  and  has  never  felt  quite  well 
since  ;  he  has  been  less  vigorous  and  has  got  somewhat  paler  and  thinner. 

In  March  last,  he  suffered  for  some  days  from  a  stabbing  pain  in  the  left  side 
(region  of  the  spleen)  ;  it  was  thought  to  be  rheumatic.    Some  six  weeks  ago,  he 

*  "British  Medical  Journal,"  23rd  July  1898,  p.  235. 


172  DISEASES   OF   THE    BLOOD. 

had  an  attack  of  diarrhoea.  Three  weeks  ago,  he  had  an  attack  of  localised 
peritonitis  ;  it  commenced  with  a  shiver  and  was  characterised  by  severe  pain 
and  tenderness  on  pressure  in  the  left  side  of  the  abdomen,  and  fever,  the  highest 
temperature  reached  being  1020  F.  A  large  tumour  was  then  found  to  be  present 
in  the  left  side  of  the  abdomen.  During  this  illness,  he  was  confined  to  bed  for 
a  fortnight  ;  as  soon  as  he  was  able  to  travel  (9th  September),  he  was  sent  to 
me,  and  I  prescribed  arsenic. 

On  lyd  September  1898,  the  patient  was  admitted  to  the  Infirmary. 

Family  history. — Unimportant. 

Present  condition. — Is  a  tall,  somewhat  spare,  man,  not  very  muscular,  though 
fairly  well  nourished.  His  complexion,  which  is  naturally  florid,  is  somewhat 
yellow  and  sallow,  but  there  is  no  marked  anaemia  to  the  naked  eye,  the  lips 
being  well  coloured.     The  temperature  is  99°  F. ;  pulse  80. 

Spleen. — The  abdomen  is  considerably  distended,  the  greater  part  of  the  left 
half  and  a  portion  of  the  right  half  of  the  cavity  being  occupied  by  a  solid  tumour 
which  presents  all  the  characteristic  features  of  an  enlarged  spleen. 

Below,  the  tumour  extends  to  within  an  inch  of  the  middle  of  Poupart's 
ligament ;  to  the  right,  it  extends  at  its  lower  end  fully  two  inches  to  the  right  of 
the  umbilicus  ;  above,  in  the  mid-axillary  line,  to  the  6th  rib  ;  to  the  left,  not 
quite  back  to  the  spinal  column. 

The  anterior  border  of  the  tumour  is  sharp  and  well  defined,  and  in  the 
anterior  border  a  very  distinct  notch  can  be  felt.  The  tumour  moves  with 
respiration  and  seems  to  overlap  the  colon.  The  tumour  is  very  firm  and  resist- 
ing ;  its  surface  appears  to  be  smooth.  Over  the  lower  end  of  the  tumour  the 
patient  still  complains  of  some  tenderness  on  pressure  (the  remains  of  the  attack 
of  peritonitis  described  above).  On  9th  September,  rough  friction  could  be 
heard  over  the  middle  part  of  the  enlarged  spleen. 

Blood. — On  microscopical  examination,  the  blood  was  found  to  contain  a  very 
large  excess  of  leucocytes,  most  of  them  of  large  size.  The  exact  character  of 
the  blood,  on  19th  September,  was  as  follows  : — 

A  drop  of  blood  obtained  by  puncturing  the  ear  looked  quite  normal  to  the 
naked  eye.  The  red  corpuscles  numbered  2,600,000  per  cubic  millimetre  ;  and 
the  haemoglobin  equalled  54  per  cent.  The  red  corpuscles  formed  rouleaux  in 
the  normal  manner  ;  and,  with  very  few  exceptions,  were  of  normal  size  and 
shape,  a  few  being  tailed  (slight  poikilocytosis),  and  a  few  larger  and  smaller 
than  normal.  In  the  numerous  stained  films  which  were  examined  I  was  only 
able  to  detect  two  nucleated  red  corpuscles  ;  one  was  of  normal  size,  the  other, 
which  contained  two  nuclei,  was  twice  the  size  of  a  normal  red  corpuscle. 

The  white  corpuscles  numbered  210,000  per  cubic  millimetre.  They  con- 
sisted almost  entirely  of  ordinary  polymorpho-nuclear  leucocytes  and  of  myelo- 
cytes ;  the  uninucleated  white  corpuscles  (lymphocytes)  were  (relatively)  much 
reduced  in  number  ;  very  few  eosinophile  cells  were  present.  In  a  few,  but  very 
few,  of  the  white  corpuscles  karyokynetic  figures  were  observed. 

On  28th  September,  the  relative  proportion  of  the  different  forms  of  white 
blood  corpuscles  was,  I  calculated  after  very  careful  counting  of  three  micro- 
scopic films,  as  follows  : — 

Polymorpho-nuclear    -         -  67  percent.  (normal  =  65  to  70  per  cent.). 

Myelocytes  -         -         -  29  per  cent,  (normal  =  0). 

Uninucleated  (lymphocytes)  3^  to  4  per  cent,  (normal  =  25  per  cent.). 

Eosinophile  cells  -         -  £  or  less  per  cent,  (normal  =i  to  4  percent.). 


LEUCOCYTHiEMIA. 


173 


Dr  Gulland  was  kind  enough  to  make  an  independent  count ;  his  results, 
which  are  practically  speaking  identical  with  my  own,  are  given  in  the  following 
table  : — 

Table  Showing  the  Percentage  of  the  Different  Forms  of 
White  Corpuscles  at  Different  Dates. 


Form  of  White  Corpuscles. 
1 

1,000  Corpuscles 
counted. 

500  Corpuscles  counted  (not 
enough  to  count  more). 

28th  Sept. 

9th  Oct. 

15th  Oct. 

2ISt  Oct. 

4th  Nov. 

Polymorpho-nuclear  neutro-  \ 
philes      -         -         -         -  J 

Per  cent. 
69 

Per  cent. 
70 

Per  cent. 
91 

Per  cent. 

75 

Per  cent. 
62 

Myelocytes  - 

26J 

25 

3 

5 

7 

Lymphocytes        - 

3* 

4 

5 

20 

3i 

Eosinophiles         -         -         - 
Total 

1 

1 

1  + 

100 

100 

100 

100 

100 

B* 

Gt 

G 

B 

G 

Nucleated  red  corpuscles. — In  the  count  of  28th  September,  there  was  one 
nucleated  red  corpuscle — a  normoblast  ;  this  was  the  only  nucleated  red  cor- 
puscle seen  in  the  whole  series  of  films. 

The  lymphatic  glands  are  not  enlarged. 

Heart. — The  apex  is  somewhat  higher  than  normal,  being  situated  in  the  4th 
interspace,  just  below  the  left  nipple.  A  soft  systolic  murmur,  not  heard  in  the 
back,  is  present  in  the  mitral  area.  A  well-marked  venous  hum  is  present  in  the 
neck.  The  pulse  numbers  80  per  minute,  and  is  soft  in  character.  The  feet  are 
slightly  swollen.  Lungs  normal.  Liver  apparently  normal  ;  in  the  line  of  the 
nipple  the  liver  dulness  extends  from  the  4th  rib  above  to  the  costal  margin 
below.  Kidneys. — The  urine  is  normal  in  quantity,  acid,  specific  gravity  1,015  '■>  it 
deposits  a  copious  sediment  of  urates  and  on  heating  throws  down  a  precipitate 
which  is  only  partly  cleared  by  the  addition  of  an  acid  (both  albumen  and 
phosphates).  No  casts  were  detected  in  the  sediment  and  in  the  course  of  a 
few  days  after  the  patient's  admission  to  hospital  the  albumen  almost  entirely 
disappeared.  The  albumen  which  was  present  on  admission  was  serum  albumen ; 
there  was  no  peptone  and  no  blood  or  sugar.  Nervous  system  normal.  The  optic 
discs  are  pale  ;  there  are  no  haemorrhages  in  the  retinae. 

Treatment. — From  the  9th  to  the  23rd  of  September,  the  patient  was  treated 
with  arsenic. 

After  his  admission  to  the  hospital,  the  arsenic  was  continued  in  gradually 
increasing  doses,  the  maximum  dose  reached  being  49  drops  per  diem. 

On  z\th  September,  mercurial  ointment  was  rubbed  over  the  spleen  ;  the 
inunctions  were  continued  daily  until  27th  October ;  no  ptyalism  or  other 
indications  of  constitutional  disturbance  resulted. 


*  B  =  Dr  Bramwell's  films. 


t  G  =  Dr  Gulland's  films. 


174  DISEASES   OF   THE   BLOOD. 

On  27///  September,  inhalations  of  carbonic  acid  gas  and  oxygen  were  com- 
menced; the  inhalations  were  given  three  times  daily,  at  first,  for  five  minutes 
at  a  time,  the  duration  of  the  inhalations  being  gradually  increased  to  half  an 
hour,  three  times  daily.  The  gas  from  a  cylinder  of  compressed  carbonic  acid 
gas  and  from  a  cylinder  of  compressed  oxygen  was  conducted  through  a  large 
bottle  of  water,  and  the  mixture  inhaled  by  the  patient.  No  perceptible  effect 
(alteration  in  colour,  or  dyspnoea,  etc.)  was  observed  as  the  result  of  the  inhala- 
tions ;  and  the  patient  stated  that  he  felt  no  difficulty  in  breathing  or  other 
uncomfortable  effects  (sensations).  On  ijth  October,  the  carbonic  acid  was 
stopped. 

Subsequent  Progress  of  the  Case. — 26th  September. — Less  pain  over  the 
enlarged  spleen. 

17th  September. — Red  corpuscles  =  2, 184,000  per  c.mm. ;  white  corpuscles  = 
130,000  per  c.mm.;  haemoglobin  =  50  per  cent. 

2gt/i  September. — -No  pain  or  tenderness  over  the  enlarged  spleen. 

5/A  October. — Complains  of  slight  pain  over  the  enlarged  spleen  ;  for  the 
past  two  days  there  has  been  some  diarrhoea  ;  the  enlargement  of  the  spleen  is 
distinctly  less. 

gtfi  October. — The  abdomen  at  the  level  of  the  umbilicus  measures  34  inches. 

20///  October. — Circumference  of  abdomen  =  30  inches;  spleen  considerably 
less  enlarged.  Red  corpuscles  =  2,300,000 ;  white  corpuscles,  6,200  per  cubic 
millimetre  ;  haemoglobin  =  60  per  cent. 

25th  October. — The  temperature  rose  to  1010  F. 

2jth  October. — Is  still  feverish  (temperature  =  102. 2°  F.)  ;  a  papular  erythema 
covers  the  abdomen,  trunk  and  upper  part  of  the  thighs  ;  tongue  slightly  furred; 
no  sore  throat.  The  red  corpuscles  have  fallen  to  1,500,000  and  the  white 
corpuscles  to  1,600  per  c.mm.;  the  haemoglobin  =  35  per  cent.  The  mercury  to 
be  discontinued. 

1st  November. — The  eruption  is  fading  ;  the  temperature  is  to-day  990,  and 
the  patient  feels  better  ;  the  enlargement  of  the  spleen  is  considerably  less.  On 
microscopical  examination,  the  freshly-drawn  (unstained)  blood  appears  to  be 
quite  normal  ;  the  red  corpuscles  are  normally  shaped,  and  the  white  corpuscles 
are  not  in  excess.  In  stained  films  the  few  white  corpuscles  which  are  present 
are  seen,  with  few  exceptions,  to  be  lymphocytes  and  polymorpho-nuclear  neutro- 
philes  ;  a  few  myelocytes  and  a  few  small  eosinophile  corpuscles  are  present. 

\th  November. — The  temperature  rose  last  night  to  103°;  the  rash  is  brighter 
and  more  extensive  to-day,  and  is  more  marked  on  the  back  of  the  trunk,  the 
limbs  and  face. 

5///!  November. — Morning  temperature  normal,  evening  temperature  103.60 ; 
pulse  114  ;  respirations  20. 

jth  November. — On  the  left  arm  and  lower  part  of  the  back  the  eruption  is 
purpuric  in  character.  The  upper  eyelids  are  much  swollen  ;  spleen  smaller  ; 
friction  heard  over  it. 

\oth  November. — Eruption  fading,  and  skin  beginning  to  desquamate  ;  face 
and  eyelids  still  swollen.  Dr  Welsh  examined  films  of  blood,  taken  from  the 
purpuric  patch  over  the  lower  part  of  the  back,  for  micro-organisms,  but  found 
none. 

\2tf1  November. — Temperature  normal  ;  very  free  desquamation  on  the  face, 
limbs  and  trunk  ;  one  or  two  small  unhealthy-looking  ulcers  on  the  sides  of  the 
tongue  ;  no  sore  throat ;  diarrhoea.  Urine  not  dark  ;  heavy  deposit  of  mucus, 
urates  ;  small  quantity  of  albumen. 


LEUCOCYTH^LMIA. 


175 


2377/  November.  —  Looking  and  feeling  much  better  ;    desquamation  still 
present  ;  eczema  of  right  ear  ;  spleen  considerably  smaller. 

The  condition  of  the  blood  at  different  dates  was  as  follows  : — 


Table  Showing  the  Condition  of  the  Blood  at  Different  Dates. 


Date. 

Red 

Corpuscles. 

Haemoglobin. 

Colour  Index 
(corrected). 

White 
Corpuscles. 

Proportion  of 

Whites  to 

Reds. 

Per  cent. 

19th  September. 

2,600,000 

54 

I.I 

210,000 

I   tO      12 

25th 

2,000,000 

56 

i-5 

200,000 

I    „       IO 

28th 

2, 1 84,000 

50 

1.2 

1 30,000 

I    „       16 

1st  October. 

I  56,000 

3rd 

2,000,000 

5o 

i-3 

109,000 

I    „       18 

9th 

81,450 

nth 

2,640,000 

56 

1.1 

62,500 

I    ,,      42 

15th 

2,070,000 

54 

1.4 

36,000 

1  „     57 

1 8th 

3,000,000 

56 

1. 

7,000 

1  „  428 

20th 

2,300,000 

60 

1.4 

6,200 

1  „  37o 

23rd 

3,000,000 

60 

1.1 

4,500 

1  „  666 

27th 

1,500,000 

35 

i-3 

1,600 

1  „  937 

3rd  November. 

2,100,000 

2,400 

1  „  875 

nth 

1,250,000 

45 

2. 

4,500 

1  „  277 

17th 

3,125,000 

5o 

.8 

2,6oO- 

1  „  1201 

Remarks. — This  case  of  spleno-medullary  leucocythaemia  presents  several 
points  of  great  interest.  The  more  important  are  : — (1)  The  small  number  of 
eosinophile  cells  ;  (2)  the  relatively  small  number  of  lymphocytes  ;  (3)  the  re- 
markable diminution  in  the  number  of  leucocytes  which  occurred  during,  and 
apparently  as  the  result  of,  the  treatment  ;  (4)  the  fact  that  when  the  leucocytes 
had  fallen  to  1,600  per  c.mm.,  some  myelocytes  were  still  present  in  the  blood  ; 
(5)  the  very  scanty  number  of  nucleated  red  corpuscles  which  were  present,  even 
when  the  leucocythaemia  was  at  its  height  ;  (6)  the  fever  and  skin  eruption 
which  occurred  during  the  course  of  the  disease,  the  cause  of  which  is  not 
apparent ;  (7)  the  great  diminution  of  the  red  corpuscles  which  occurred  as  the 
result  of  this  febrile  attack ;  (8)  the  absence  of  any  leucocytosis  during  the  febrile 
attack;  (9)  the  fact  that  the  individual  red  corpuscles  contained  more  than  the 
normal  amount  of  haemoglobin  (high  colour-index) ;  in  this  respect  the  condition 
of  the  blood  resembled  that  of  pernicious  anaemia. 


HODGKIN'S    DISEASE. 

Definition  or  Short  Description. — The  essential  features  of 
Hodgkin's  disease,  to  which  the  synonyms  Lymphatic  Anamiia, 
Lymphadenosis,  P  seudoleukcemia,  Malignant  Lymphoma,  Lympha- 
denoma,  Adc'nie,  Lymph-adenie,  etc.,  have  been  applied,  are  : — (i)  A 
widespread  non-caseating  and  non-suppurating  enlargement  of  the 
lymphatic  glands  (a  generalised  hypertrophy  of  the  lymphatic 
glands,  Trousseau  termed  it) ;  and  (2)  certain  constitutional 
symptoms,  amongst  which  weakness  and  emaciation  are  the  most 
important. 

In  the  advanced  stages  of  the  disease,  nodules  or  deposits,  as 
they  have  been  termed,  of  adenoid  or  lymphoid  tissue  may  be 
developed  in  the  spleen  and  other  parts  of  the  body,  in  which 
adenoid  or  lymphoid  tissue  normally  abounds  (tonsils,  solitary 
glands  of  the  intestine,  Peyer's  patches,  thymus  gland,  etc.),  and, 
in  some  cases,  in  organs  and  tissues  in  which  adenoid  tissue  is 
only  very  sparingly  present,  or  is  not  present,  normally  (liver, 
kidney,  suprarenal  capsules,  skin,  etc.). 

Enlargement  of  the  spleen  is  a  clinical  feature  of  the  disease, 
which  is  of  considerable  diagnostic  importance.  A  certain  amount 
of  anaemia  is  present  in  most  cases  of  the  disease,  at  some  period 
or  other  of  their  course  ;  but,  in  other  cases  (though  this,  perhaps, 
only  occurs  at  certain  stages  of  the  case),  the  red  blood  corpuscles 
are  more  numerous  than  normal. 

In  some  cases,  in  which  the  glandular  enlargements  and  con- 
stitutional symptoms  characteristic  of  Hodgkin's  disease  are 
present,  the  blood  contains  a  large  excess  of  white  corpuscles. 
Some  authorities  regard  cases  of  this  kind  as  cases  of  Hodgkin's 
disease  to  which  lymphatic  leucocythaemia  has  been  superadded  ; 
but,  as  I  have  already  pointed  out,  the  correctness  of  this  opinion 
is,  in  many  cases  at  all  events,  extremely  doubtful. 

Hodgkin's  disease  is  usually  a  chronic,  progressive,  and  incurable 
condition,  though  acute  cases,  and  cases  which  end  in  recovery, 
occasionally  occur. 

Future  observation  will   probably  show  that  several  different 


HODGKIN  S   DISEASE.  1 77 

conditions  have  hitherto  been  grouped  together  under  the  common 
term  Hodgkin's  disease ;  in  other  words,  it  is  highly  probable  that 
more  than  one  morbid  process  may  produce  the  group  of  clinical 
symptoms  (the  form  of  enlargement  of  the  lymphatic  glands  and 
the  constitutional  symptoms)  which  are  supposed  to  be  charac- 
teristic of  Hodgkin's  disease.  By  this  statement  I  do  not  mean  to 
imply  that  Hodgkin's  disease  is  not  a  definite  and  distinct  clinical 
entity;  but  merely  to  emphasise  the  great  difficulty  of  recognising 
the  condition  during  life,  and  of  distinguishing  the  clinical  entity, 
which  we  term  Hodgkin's  disease,  from  the  other  conditions  which 
more  or  less  closely  resemble  it. 

Historical  Note. — Cases  of  this  interesting  disease  had  been 
described  before  the  year  1832  ;  indeed,  Hodgkin  himself  refers  to 
two  cases  figured  by  Carswell,  and  termed  by  him  "  Cancer  cerebri- 
formis  of  the  lymphatic  glands  "  ;  but  it  was  not  until  Hodgkin 
published  his  important  paper,  "  On  some  Morbid  Appearances  of 
the  Absorbent  Glands  and  Spleen,"  that  the  distinctive  features  of 
the  disease  were  definitely  recognised,  that  the  relationship  of  the 
enlargement  of  the  lymphatic  glands  with  disease  of  the  spleen 
was  appreciated,  and  that  the  peculiar  form  of  the  glandular 
enlargement  which  characterises  the  disease  was  differentiated  from 
the  scrofulous  and  cancerous  enlargements  of  the  lymphatic  glands 
with  which  it  had  been  previously  confounded.* 

Hodgkin  described  the  glandular  enlargement  in  the  following 
terms  : — 

"  It  may  be  observed  that  notwithstanding  some  differences  in  structure,  to 
be  noticed  hereafter,  all  these  cases  agree  in  the  remarkable  enlargement  of  the 
absorbent  glands  accompanying  the  larger  arteries — namely,  the  glandulae 
concatenate  in  the  neck,  the  axillary  and  inguinal  glands,  and  those  accom- 
panying the  aorta  in  the  thorax  and  abdomen.  That,  as  far  as  could  be  ascer- 
tained from  observation,  or  from  what  could  be  collected  from  the  history  of  the 
cases,  this  enlargement  of  the  glands  appeared  to  be  a  primitive  affection  of 
those  bodies  rather  than  the  result  of  an  irritation  propagated  to  them  from 
some  ulcerated  surface  or  other  inflamed  texture,  through  the  medium  of  their 
inferent  vessels,  and  that  although,  in  some  instances,  the  glands  so  enlarged 
may  contain  a  little  concrete  inorganisable  matter,  such  as  is  known  to  result 
from  what  is  called  scrofulous  inflammation,  it  is  obvious  that  this  circumstance 
is  not  an  essential  character,  but  rather  an  accidental  concomitant  to  the  idio- 
pathic interstitial  enlargement  of  the  absorbent  glandular  structure  throughout 
the  body.     That  unless  the  word  inflammation  be  allowed   to  have  a   more 


*  As  I  have  already  pointed  out,  the  distinction  between  the  glandular 
enlargements  due  to  Hodgkin's  disease  and  to  scrofula  is  by  no  means  so 
certain,  during  life,  as  this  statement  implies. 

M 


VJ%  DISEASES   OF   THE   BLOOD   GLANDS. 

indefinite  and  loose  meaning  than  is  generally  assigned  to  it,  this  affection  of  the 
glands  can  scarcely  be  attributed  to  that  cause,  since  they  are  unattended  with 
pain,  heat,  and  other  ordinary  symptoms  of  inflammation,  and  are  not  necessarily 
accompanied  by  any  alteration  in  the  cellular  and  other  surrounding  structures, 
and  do  not  show  any  disposition  to  go  on  to  the  production  of  pus  or  any  other 
acknowledged  product  of  inflammation,  except  where,  as  in  the  cases  above 
alluded  to,  inflammation  may  have  supervened  as  an  accidental  affection  of  the 
hypertrophied  structure.  Nor  can  the  enlargement  in  question,  with  any  better 
reason,  be  attributed  to  the  formation  of  any  of  those  adventitious  structures, 
the  production  of  which  I  have  already  had  occasion  to  describe,  and  have 
referred  to  the  type  of  compound  adventitious  serous  cysts.  Notwithstanding 
the  different  characters  which  this  enlargement  may  present,  it  appears,  nearly 
in  all  cases,  to  consist  of  pretty  uniform  texture  throughout,  and  this  rather  to 
be  the  consequence  of  a  general  increase  of  every  part  of  the  gland  than  of  a 
hard  structure  developed  within  it,  and  pushing  the  original  structure  aside,  as 
when  ordinary  tuberculous  material  is  deposited  in  these  bodies.  At  the  same 
time,  it  must  be  admitted  that  the  new  material  by  which  the  enlargement  is 
effected  presents  various  degrees  of  organisability,  which  in  some  instances  is 
extremely  slight,  and  appears  incompetent  to  maintain  the  vitality  of  the  affected 
gland.  In  such  cases  the  new  structure  will  generally  become  opaque,  soften, 
or  break  down,  and,  acting  as  a  foreign  irritating  body,  excite  irritation  and  lead 
to  the  formation  of  abscess."  * 

Since  the  year  1832,  numerous  important  papers  and  mono- 
graphs have  been  written  on  the  subject,  some  of  the  most  valuable 
being  contributed  by  physicians  in  this  country.  In  the  year  1855, 
Sir  Samuel  Wilks  independently  described  the  disease  in  a  paper 
entitled,  "  Cases  of  a  Peculiar  Enlargement  of  the  Lymphatic 
Glands  frequently  associated  with  Disease  of  the  Spleen."  f  In  a 
subsequent  communication,  he  proposed  to  give  the  name 
"  Hodgkin's  Disease"  to  the  disease.  \  Lymphatic  anaemia  is 
another  term  which  the  same  authority  (Wilks)  has  applied  to  the 
disease.  Bonfils  and  Trousseau,  whose  descriptions  of  the  disease 
are  of  great  value  and  importance,  applied  the  term  Adenie  to  it. 
One  of  the  best  accounts  of  the  disease  in  any  language  is  that  of 
Gowers,  in  Russell  Reynolds'  System  of  Medicine  (vol.  v.,  p.  306). 

Hodgkin's  disease,  or  true  lymphadenoma  (provided  that  the 
tubercular  cases  which  are  apt  to  be  confounded  with  it  are  rigidly 
excluded),  is  probably  a  very  rare  disease.  In  my  series  of  14,777 
consecutive  cases  of  medical  disease,  12  cases  were  diagnosed  as 
Hodgkin's  disease  ;  but  I  have  no  doubt  that  in  some  of  these 
cases  the  glandular  enlargement  was  in  reality  tubercular. 


*  "  Medico-Chirurgical  Transactions,"  vol.  xvii.,  p.  85. 
t  Guy's  Hospital  Reports,  vol.  ii.  (1855),  p.  131. 
+  Guy's  Hospital  Reports,  vol.  xi.  (1855),  p.  56. 


hodgkin's  disease.  179 

Morbid  Anatomy. 

As  has  been  previously  stated,  the  essential  lesion  in  Hodgkin's 
disease  is  a  peculiar  enlargement  of  the  lymphatic  glands,  together 
with,  in  many  cases,  the  development  of  deposits  of  lymphoid  or 
adenoid  tissue  in  the  spleen  and  other  organs  and  tissues  of  the 
body.  Whether  the  presence  of  lymphoid  deposits  in  the  spleen 
or  other  organs  and  tissues  is  a  necessary  and  essential  feature  of 
the  disease  is  perhaps  a  debatable  point ;  in  other  words,  it  is 
questionable  whether  only  those  cases  should  be  considered  to  be 
cases  of  Hodgkin's  disease  in  which,  in  addition  to  the  enlargement 
of  the  lymphatic  glands,  lymphoid  deposits  are  present  in  the 
spleen  and  other  organs  and  tissues. 

The  Condition  of  the  Lymphatic  Glands. — -The  extent  and 
distribution  of  the  glandular  enlargement  varies  in  different  cases. 
In  some  cases,  all  the  glands  in  the  body  (external  and  internal) 
are  involved,  and  lymphatic  glands  may  become  apparent  in  situa- 
tions (such  as  the  popliteal  space  and  at  the  bend  of  the  elbow)  in 
which  they  cannot  be  detected  (during  life)  in  conditions  of  health. 
In  other  cases,  the  glandular  involvement  is  less  extensive ;  but,  as 
has  already  been  pointed  out,  the  glandular  enlargement  is  not 
merely  local  (confined,  for  example,  to  the  cervical  glands),  as  a 
scrofulous  enlargement  usually  is. 

The  size  to  which  the  individual  glands  and  glandular  masses 
may  attain  is  very  variable. 

In  many  cases,  the  individual  glands  remain  separate  and  dis- 
tinct ;  in  other  cases,  the  enlarged  glands  are  firmly  adherent,  and 
matted  or  welded  together  in  the  form  of  large  masses  or  tumours. 
In  cases  of  this  kind,  various  secondary  alterations  and  lesions  due 
to  pressure,  inflammation,  or  infiltration  may  be  developed  in  the 
tissues  and  organs  with  which  the  masses  of  enlarged  glands  are  in 
contact.  When,  for  example,  the  bronchial  and  mediastinal  glands 
are  enlarged,  the  root  of  the  lung,  the  lung  tissue  itself,  the  great 
veins  in  the  thorax,  the  recurrent  laryngeal  nerve,  etc.,  may  be 
implicated  ;  or  pleurisy  and  empyema  may  be  developed. 

The  consistency  of  the  enlarged  glands  varies  in  different  cases. 
In  most  cases,  the  enlarged  glands  are  firm,  though  they  have  not 
the  stony  hardness  of  the  enlargement  due  to  cancer  ;  in  other 
cases,  the  consistency  is  softer.  Consequently,  two  varieties — a 
hard  and  a  soft  form — -are  described. 

To  the  naked  eye,  the  character  of  the  glandular  enlargement  is 
very  similar  to  that  which  occurs  in  the  lymphatic  form  of  leucocy- 
thaemia. 


ISO  DISEASES   OF   THE   BLOOD   GLANDS. 

On  section,  in  both  the  hard  and  the  soft  varieties,  the  enlarged 
glands  present  a  more  or  less  homogeneous  appearance  ;  there  is 
usually  no  appearance  of  softening,  breaking  down,  caseation,  or 
suppuration.  In  well-marked  and  typical  cases  of  the  disease,  the 
distinction  between  the  cortical  and  medullary  portions  of  the  gland 
can  no  longer  be  recognised. 

But  it  is  important  to  note  that,  although  in  typical  cases  of 
Hodgkin's  disease  the  glandular  enlargements  present  the  patholo- 
gical characters  which  have  just  been  described,  in  some  cases  in 
which  the  glandular  enlargements  during  life  present  all  the  charac- 
teristic clinical  features  of  Hodgkin's  disease,  the  enlarged  glands 
are  found  after  death  to  be  caseous  and  tubercular.  I  have  seen 
several  cases  of  this  kind,  and  I  have  been  so  impressed  with  the 
difficulty  that  there  is  in  some  cases,  more  especially  in  children 
and  in  young  subjects,  of  differentiating  during  life  the  glandular 
enlargements  due  to  Hodgkin's  disease  from  that  due  to  tubercle, 
that  I  now  have  great  hesitation  in  committing  myself  to  a  definite 
diagnosis  of  Hodgkin's  disease  and  in  excluding  tubercle,  unless 
the  spleen  is  distinctly  enlarged,  or  unless  there  is  evidence  of  the 
presence  of  lymphoid  deposits  in  the  other  organs  and  tissues.  It 
is  certain,  I  think,  that  the  frequency  with  which  enlarged  glands, 
which  during  life  present  all  the  appearances  characteristic  of 
Hodgkin's  disease,  are  found  after  death  to  be  tubercular  has  been 
much  under-estimated. 

On  microscopical  examination,  it  is  seen  that,  in  typical  cases, 
the  affected  glands  are  for  the  most  part  composed  of  small  round 
cells,  resembling  leucocytes  or  ordinary  lymph  cells,  and  of  fibrous 
tissue,  arranged  in  the  form  of  a  network  or  in  trabecular.  A  few 
large  multi-nucleated  corpuscles  are  in  some  cases  also  present,  and 
the  presence  of  myelocytes  and  nucleated  red  blood  corpuscles  have 
in  exceptional  cases  been  described. 

The  relative  proportion  of  the  cells  to  the  fibroid  tissue  varies 
in  different  cases.  In  the  soft  variety,  the  whole  section  may,  at 
first  sight,  appear  to  be  composed  of  cells,  the  delicate  fibrous  net- 
work, in  the  meshes  of  which  the  cells  are  situated,  being  only  seen 
after  special  methods  of  preparation  (pencilling  or  teasing).  In 
the  hard  variety,  the  fibrous  tissue  is  relatively  much  more  abun- 
dant ;  the  fibrous  septa  of  the  gland  are  thickened,  and,  in  some 
cases,  dense  bands  of  fibrous  tissue  may  be  seen  crossing  the 
section  in  various  directions,  and  forming  the  trabecular  structure 
described  above. 

In  some  cases,  spindle  cells  with  oval  nuclei  are  present  in 
addition  to  the  ordinary  fibroid  elements. 


hodgkin's  disease.  181 

Spleen.— In  the  great  majority  of  cases  of  Hodgkin's  disease, 
the  spleen  is  enlarged,  though  the  enlargement  is  not  as  a  rule 
very  great. 

In  most  cases,  the  enlargement  of  the  spleen  is  due  to  localised 
deposits  of  lymphoid  tissue,  which  look  like  whitish  nodules  or 
masses  of  suet  or  bacon-fat,  deposited  here  and  there  in  the  splenic 
substance.  The  nodules  in  the  spleen  are  for  the  most  part  due  to 
pathological  alterations  in  the  Malpighian  bodies  (lymphoid  tissue), 
similar  in  nature  to  those  which  are  present  in  the  lymphatic 
glands. 

In  some  cases,  the  enlargement  of  the  spleen  is  uniform,  and  no 
lymphoid  deposits  are  visible  to  the  naked  eye. 

Liver. — The  liver  is  in  some  cases  enlarged,  and  studded  with 
lymphoid  deposits. 

Lymphoid  deposits  in  other  organs  and  tissues. — Lymphoid 
deposits  and  nodules  are  frequently  developed  in  the  gastro- 
alimentary  tract,  especially  in  the  stomach  and  the  small  intestine 
(the  Peyer's  patches  and  solitary  glands  are  very  apt  to  be  affected)  ; 
and  are  sometimes  seen  at  the  back  of  the  tongue,  in  the  tonsils,  and 
even  in  the  walls  of  the  oesophagus. 

The  thymus  gland  is  in  some  cases  enlarged  and  infiltrated  with 
lymphoid  cells.  Lymphoid  deposits  and  nodules  may  also  be 
present  in  the  marrow  of  the  bones,  kidneys,  suprarenal  capsules, 
thyroid  gland,  heart,  pleura,  ovary,  skin,  etc. 

The  deposits  of  lymphoid  tissue  in  the  spleen,  liver,  and 
other  organs,  present  the  same  histological  characters  as  those 
which  are  present  in  the  enlarged  glands  themselves  ;  in  other 
words,  they  consist  of  lymphoid  cells  embedded  in  a  fibrous 
reticulum. 

In  some  cases,  the  vessels  of  the  enlarged  glands,  of  the  spleen, 
liver,  kidney,  etc.,  present  evidences  of  waxy  (amyloid)  degeneration ; 
but  the  waxy  change  is  not  usually  extensive. 

Bone-marrow. — The  changes  in  the  bone-marrow,  when  they 
occur,  appear  to  be  very  similar  to  those  which  occur  in  the  lym- 
phatic form  of  leucocythaemia  ;  but,  so  far  as  I  know,  it  has  not 
yet  been  shown  that  the  character  of  the  leucocytes  which  infil- 
trate the  bone-marrow  in  the  two  affections  is  identical.  As  has 
been  already  stated,  I  am  disposed  to  think  that  Hodgkin's  disease 
and  the  lymphatic  form  of  leucocythaemia  are  distinct  conditions, 
and  that  this  statement  applies  to  most  of  the  cases  of  Hodgkin's 
disease,  at  all  events,  in  which  the  blood  contains  an  excess  of 
white  corpuscles. 


1 82  diseases  of  the  blood  glands. 

Etiology  and  Pathology. 

Age. — Hodgkin's  disease  may  occur  at  any  age,  but  is  most 
common  during  childhood,  youth,  and  early  adult  life.  Of  ioo 
cases  tabulated  by  Gowers,  50  occurred  before  the  age  of  30,  and 
64  before  the  age  of  40.  In  my  series  of  12  cases,  7  (or  56  per  cent.) 
occurred  before  the  age  of  30,  and  8  (or  66  per  cent.)  occurred  before 
the  age  of  40. 

Sex. — Males  are  much  more  frequently  affected  than  females. 
In  the  100  cases  analysed  by  Gower,  75  were  males,  and  25  were 
females.  In  my  series  of  12  cases,  10  (or  83  per  cent.)  were  males, 
and  2  (or  16  per  cent.)  were  females.  From  these  figures  it  would 
therefore  appear  that  the  disease  is  at  least  three  times  as  common 
in  the  male  as  in  the  female. 

Influence  of  depressing  circumstances,  etc.  —  Depressing 
influences  of  all  kinds,  such  as  previous  ill-health,  insufficient  food, 
deficient  clothing,  insanitary  surroundings,  intemperance,  mental 
anxiety,  etc.,  seem  to  favour  the  production  of  the  disease,  but 
they  are  clearly  only  predisposing  causes.  In  some  cases,  the 
disease  is  developed  in  the  midst  of  perfect  health,  in  persons 
who  have  never  previously  had  any  severe  illness,  and  in  those 
whose  sanitary  surroundings  and  circumstances  are  altogether 
satisfactory.  Malaria  and  rickets  have  in  some  cases  been  thought 
to  be  causes  of  the  disease.  Syphilis  does  not  appear  to  be  a  cause 
of  the  disease.  In  some  cases,  the  subjects  of  Hodgkin's  disease 
have  previously  suffered  from  scrofulous  enlargement  of  the  lym- 
phatic glands,  or  have  inherited  a  strong  tendency  to  scrofula ;  but 
whether  there  is  any  real  relationship  between  scrofula  and 
Hodgkin's  disease  (true  lymphadenoma)  is  doubtful.  In  a  few 
(apparently  exceptional)  cases,  active  tubercular  lesions  have  been 
found  in  the  lungs  or  other  organs  after  death  ;  but  whether  all  of 
these  cases  were  in  reality  Hodgkin's  disease  (true  lymphadenoma) 
is  I  think  very  doubtful  ;  for,  as  I  have  already  stated,  cases  are 
not  unfrequently  met  with,  especially  in  young  subjects,  in  which 
the  clinical  symptoms  and  the  condition  of  the  enlarged  glands 
during  life  were  typically  those  of  Hodgkin's  disease  rather  than  of 
scrofula,  but  in  which  post-mortem  examination  showed  that  the 
glandular  enlargement  was  without  doubt  tubercular. 

Probable  exciting  cause. — The  exact  condition  or  condi- 
tions which  produce  Hodgkin's  disease  are  as  yet  entirely  unknown. 
On  theoretical  grounds  it  is  not  unreasonable,  I  think,  to  suppose 
that  the  disease  is  due  to  the  presence  in  the  blood  of  some  sub- 
stance or  substances  which  excite  the  overgrowth  or  development 


hodgkin's  disease.  183 

of  lymphoid  tissue — possibly  some  chemical  substance  (irritant) 
produced  within  the  body,  or  some  chemical  or  germ  poison  or  its 
toxin  introduced  from  without. 

Or  perhaps  the  essential  cause  of  the  disease  consists  in  some 
peculiarity  of  constitution,  inherited  or  acquired,  which,  in  the 
subjects  of  Hodgkin's  disease,  favours  the  production  of  an  over- 
growth of  lymphoid  tissue,  or  allows  some  irritant,  which  in  ordinary 
healthy  individuals  would  be  inoperative,  to  excite  the  production 
of  a  lymphatic  overgrowth. 

In  some  cases,  more  especially  in  some  of  the  cases  in  which 
generalised  lymphatic  enlargement  is  preceded  by  a  strictly  local 
glandular  enlargement,  local  irritation  seems  to  be  the  exciting 
cause  of  the  primary  (local)  glandular  swelling.  In  one  of  my  own 
cases,  chronic  irritation  and  inflammation  in  the  nose,  and  in  another 
of  the  throat,  seemed  undoubtedly  to  be  the  starting-point  of  the 
condition.  In  both  of  these  cases  the  cervical  glands  were  first 
enlarged.  The  influence  of  local  peripheral  irritation  in  exciting 
the  primary  glandular  enlargement  has  been  especially  insisted 
upon  by  Trousseau.  In  speaking  of  the  etiology  of  the  disease, 
he  says  :* — ■ 

"  We  are  thus  constrained  to  conclude  that  there  is  a  new  special  diathesis, 
the  essential  nature  of  which  is  unknown,  which  we  call  the  lymphatic  diathesis. 
This  diathesis  may  be  described  as  a  tendency  in  certain  persons  to  present, 
under  the  influence  of  a  determining  cause,  glandular  engorgements,  at  first 
local,  and  becoming  general  in  from  eighteen  months  to  two  years.  This  glan- 
dular engorgement,  as  I  have  seen,  may  consist  in  a  hypergenesis  of  the  normal 
cellular  elements  of  the  lymphatic  glands,  a  hypergenesis  which  in  some  cases 
may  invade  the  glandular  corpuscles  of  the  spleen  and  intestine.  The  patient, 
consequently,  has  anaemia  and  cachexia,  unaccompanied  by  leucocytosis. 

"  Adenia,  I  have  said,  is  a  diathesis  which  has  a  determining  cause.  What 
is  this  cause,  and  what  is  its  most  common  seat  ?  When  we  attentively  peruse 
the  reports  of  cases  of  adenia,  whether  described  by  others  or  observed  by  our- 
selves, we  are  struck  by  the  fact  that,  in  the  first  instance,  only  one  or  two 
glands  have  been  enlarged  :  some  weeks,  or  it  may  be  two  or  three  months, 
after  the  appearance  of  these  swellings,  a  veritable  explosion  of  glandular 
tumours  occurs  in  different  parts  of  the  body,  while,  at  the  same  time,  the 
original  tumours  rapidly  increase  in  size.  In  the  majority  of  cases  the  sub- 
maxillary are  the  glands  which  first  become  affected  :  sometimes,  however,  the 
first  seat  of  the  affection  is  in  the  axillary  or  inguinal  glands. 

"Whenever  there  is  an  acute  or  chronic  engorgement  of  glands,  we  must 
search  in  the  regions  which  they  depurate  for  some  organic  lesion  to  explain  the 
glandular  irritation.  This  rule,  which  is  absolute,  will  be  found  to  lead  to  many 
important  results.  It  is  natural,  therefore,  in  a  case  of  general  adenia,  to  inquire 
what  local  lesion  has  occasioned  the  original  engorgement.  There  are  many 
cases,  however,  in  which  no  light  is  thrown  upon  this  question  :  we  must  be 

*  "  Clinical  Medicine,"  Sydenham  Society's  Edition,  vol.  v.,  p.  206. 


1 84  DISEASES   OF   THE   BLOOD   GLANDS. 

satisfied  to  note  that  the  engorgement  commenced  in  the  axillary,  inguinal,  or 
maxillary  glands — which  is  provoking.  Viewed  along  with  these  incomplete 
cases,  there  are  others — the  cases  of  Leudet,  Potian,  and  Perrin,  and  the  case  of 
my  Stockholm  patient — which  possess  great  interest  in  relation  to  this  question. 
I  have  thrice  observed  that  there  existed  acute  or  chronic  irritation  at  the  great 
angle  of  the  eye,  or  in  the  external  auditory  passage  :  and  observe,  Gentlemen, 
that  the  glands  first  attacked  were  situated  on  the  same  side  as  the  ocular,  nasal, 
or  aural  lesion,  and  that  the  submaxillary  and  cervical  glands  of  the  opposite 
side,  as  well  as  the  other  glands  of  the  body,  were  only  secondarily  attacked. 
It  is,  therefore,  well  worthy  of  remark  that,  in  the  five  cases  to  which  I  have 
referred,  there  were  four  with  inflammatory  lachrymal  tumour,  chronic  coryza, 
and  otorrhcea.  One  cannot  help  being  struck  with  this  alteration  of  the  skin 
and  mucous  membranes,  and  with  the  primary  glandular  alteration.  I  ought, 
however,  to  remind  you  that,  in  one  of  Leudet's  cases,  and  also  in  the  case  for 
which  we  are  indebted  to  Perrin,  the  patients  stated  that  the  glandular  engorge- 
ment began  in  the  axillary  region.  Subsequently,  however,  MM.  Leudet  and 
Perrin  discovered  submaxillary  engorgement,  so  that  we  may  suppose  the 
possibility  of  that  engorgement  having  existed  at  the  commencement  of  the 
adenia,  but  to  so  small  an  extent  as  not  to  attract  the  notice  of  the  patients. 

"  Be  that  as  it  may,  it  is  a  fact  that,  in  twelve  cases  of  adenia,  there  were  four 
in  which,  there  existed  lachrymal  tumours,  a  chronic  coryza,  and  an  otorrhcea. 

"  It  is  not  a  matter  involved  in  the  least  doubt — it  is  a  positive  fact — that 
there  is  a  relation  between  the  primary  adenopathia  and  the  superficial  lesions 
of  skin  and  mucous  membrane. 

"As  to  general  consecutive  adenia,  I  cannot  understand  admitting  certain 
persons  to  have  a  predisposition  to  such  a  special  nature,  that  one  or  two 
lymphatic  glands  being  engorged  for  a  certain  short  period,  in  general  of 
variable  duration,  but  nearly  always  of  recent  date,  should  be  the  starting-point 
of  the  generalisation  of  the  malady  to  the  other  glands." 

In  some  cases  of  Hodgkin's  disease,  micro-organisms  have  been 
detected  in  the  blood  ;  in  others,  in  which  a  careful  search  has  been 
made,  no  micro-organisms  have  been  found.  The  probability  that 
the  glandular  enlargement  is  due  to  some  form  of  irritation  is  very- 
great,  and  the  occurrence  of  acute  cases,  such  as  those  described  by 
Dreschfeld,  and  the  frequent  development  of  fever  in  the  course  of 
the  disease  lend  support  to  this  supposition.  Further  information 
and  observation  on  this  point  are,  however,  required.  In  the  pre- 
sent position  of  our  knowledge  I  do  not  think  one  is  warranted  in 
going  further  than  this,  that  the  theory  which  supposes  that  some 
of  the  conditions  which  are  at  present  grouped  together  under  the 
common  term  Hodgkin's  disease  are  due  to  micro-organisms  or 
their  toxins  is  probable,  but  as  yet  not  proven. 

The  exact  nature  of  Hodgkin's  disease,  or  rather  of  the  condi- 
tions which  may  produce  the  group  of  clinical  symptoms  character- 
istic of  Hodgkin's  disease,  will  be  further  considered  in  connection 
with  the  clinical  history,  the  clinical  types,  and  the  diagnosis  of  the 
disease. 


hodgkin's  disease.  185 

Clinical  History. 

Onset  and  Course. — The  onset  is  usually  slow  and  gradual, 
and  the  course  usually  chronic  and  progressive,  though  in  some 
cases  periods  of  distinct  improvement  occur.  In  rare  cases,  the 
onset  is  rapid  and  the  course  acute.  A  number  of  cases  of  this 
kind  have  been  recorded  by  Dreschfeld  and  other  observers. 

Clinical  Features.— The  symptoms  which  characterise  Hodg- 
kin's disease  (and  the  symptoms  and  physical  signs  which  result 
from  the  glandular  enlargements  which  are  the  essential  feature  of 
the  disease)  are  partly  local  and  partly  constitutional.  The  more 
important  may  be  classed  as  follows  : — 

1.  Enlargement  of  the  lymphatic  glands — visible,  tangible,  or  de- 
monstrable by  means  of  physical  examination  {e.g.,  percussion,  etc.). 

2.  Weakness,  emaciation,  cachexia,  and  symptoms  associated 
therewith. 

3.  Anaemia — diminution  of  the  red  blood  corpuscles,  with,  in 
some  cases,  an  excess  of  white  blood  corpuscles — and  the  symptoms 
which  result  therefrom. 

4.  Loss  of  appetite,  dyspepsia,  and  other  symptoms  indicative 
of  derangement  of  the  gastro-intestinal  functions. 

5.  Pyrexia. 

6.  Enlargement  of  the  spleen. 

7.  Enlargement  of  the  tonsils,  of  the  liver,  and  it  may  be  of  other 
internal  organs,  such  as  the  thymus  gland  or  suprarenal  capsules. 

8.  Symptoms  and  physical  signs  due  to  the  pressure  of  the 
enlarged  lymphatic  glands  upon  adjacent  structures  and  parts. 

9.  Symptoms  and  physical  signs  due  to  inflammatory  com- 
plications in  the  neighbourhood  of  the  enlarged  glands,  and  to 
associated  lesions. 

It  must  be  clearly  and  definitely  understood  that  all  of  the 
symptoms  and  clinical  alterations,  which  have  just  been  enumerated, 
are  by  no  means  always  present.  The  clinical  picture  which  dif- 
ferent cases  of  Hodgkin's  disease  present  is,  in  fact,  a  very  variable 
one.  This  is  only  what  one  might  expect  from  the  fact  that  the 
symptoms  and  physical  signs,  which  are  due  to  the  pressure  which 
the  enlarged  glands  exert  upon,  and  the  inflammation  which  the 
enlarged  and  diseased  glands  excite  in,  the  tissues  and  organs  with 
which  they  are  in  immediate  contact,  necessarily  vary  in  different 
cases  ;  and  to  the  circumstance  that  more  than  one  different  patho- 
logical condition  may  probably  produce  very  similar  clinical  results, 
viz.,  glandular  enlargements  and  constitutional  symptoms  suggestive 
of  Hodgkin's  disease. 


1 86  DISEASES   OF   THE    BLOOD   GLANDS. 

The  only  clinical  symptoms  which  can  be  regarded  as  constant, 
though  they  are  not  pathognomonic,  for  they  occur  in  some  cases 
in  which  the  glandular  affection  is  tubercular,  are—; firstly ',  enlarge- 
ment (not  a  mere  local  but  a  more  or  less  widespread  enlargement) 
of  the  lymphatic  glands  ;  and,  secondly,  weakness,  emaciation,  and 
(usually)  more  or  less  anaemia. 

But  even  with  regard  to  these  symptoms,  it  must  be  remembered 
that,  in  some  cases,  which  appear  to  be  undoubted  cases  of  Hodg- 
kin's  disease,  the  internal  lymphatic  glands  are  chiefly,  or  almost 
exclusively,  affected,  and  that  in  such  cases  a  visible  and  tangible 
enlargement  of  the  lymphatic  glands  may  not  be  present ;  and 
that,  in  other  cases,  even  when  the  enlargement  of  the  lymphatic 
glands  is  widespread  and  well  marked,  there  is  little  or  no  anaemia 
— little  or  no  diminution  in  the  number  of  the  red  blood  corpuscles 
as  measured  by  the  haemocytometer,  in  fact  in  some  cases  the 
number  of  red  blood  corpuscles  is  increased.  Some  diminution 
of  the  red  blood  corpuscles  is,  however,  usually  present,  when 
the  disease  is  fully  developed,  and  it  is  probable  that  a  certain 
degree  of  anaemia  is  met  with  in  all  typical  cases  of  Hodgkin's 
disease,  at  some  period  or  other  of  their  coarse. 

In  typical  cases  of  Hodgkin's  disease,  the  spleen  is  usually 
enlarged  ;  and  pyrexia  is  generally  present.  An  excess  of  white 
corpuscles  in  the  blood  is  observed  in  a  certain  proportion  of  cases. 

The  symptoms  and  physical  signs  due  to  pressure  and  to  local 
inflammations  in  the  neighbourhood  of  the  enlarged  glands  are 
inconstant,  and  may  in  fact  be  termed  accidental  symptoms. 

It  may  be,  and  indeed  it  has  been,  questioned  whether  those 
cases  in  which  the  internal  lymphatic  glands  (such  as  the  medias- 
tinal, bronchial,  and  retro-peritoneal  glands)  are  alone  involved,  are 
actually  cases  of  Hodgkin's  disease. 

As  I  have  more  than  once  pointed  out,  it  is  probable  that  more 
than  one  form  of  lymphatic  enlargement  is  included  under  the 
common  term  Hodgkin's  disease  ;  though  in  the  present  position  of 
our  knowledge  we  are  unable  to  differentiate  these  different  varie- 
ties of  glandular  enlargement  in  the  living  patient,  and  perhaps  not 
even  in  the  dead-house.  Perhaps  the  most  satisfactory  statement 
which  can  at  present  be  made  with  regard  to  the  glandular  enlarge- 
ment is  this  : — that  only  those  glandular  enlargements  should  be 
considered  as  characteristic  of  Hodgkin's  disease  in  which  several 
different  groups  of  lymphatic  glands  are  affected,  and  in  which  the 
glandular  enlargement  is  painless,  non-suppurating,  and  non- 
caseating.  But  even  this  definition  is  not  altogether  satisfactory  ;  for 
(i)  in  some  cases  which,  so  far  as  our  present  means  of  observation 


hodgkin's  disease.  187 

enable  us  to  judge,  are  cases  of  Hodgkin's  disease,  the  enlarged 
lymphatic  glands  do  soften  and  ulcerate ;  and  (2)  in  some  cases  in 
which  the  glandular  enlargement  is  widespread,  painless,  and  non- 
suppurating,  the  condition  is  tubercular. 

From  these  statements,  and  from  what  I  have  previously  stated 
in  connection  with  the  pathology  and  etiology  of  the  disease,  it  will 
be  obvious  that  our  knowledge  of  the  true  nature  of  Hodgkin's 
disease  is  in  a  very  unsettled  and  unsatisfactory  condition. 

As  I  have  already  pointed  out  in  the  article  on  leucocythasmia, 
I  am  strongly  inclined  to  think  that  Hodgkin's  disease  and  lymphatic 
leucocythaemia  are  separate  and  distinct  conditions. 

Let  us  now  consider  the  chief  symptoms  of  Hodgkin's  disease 
individually  and  in  detail. 

Enlargement  of  the  Lymphatic  Glands. — As  I  have  already 
pointed  out,  this  is  the  fundamental  and  characteristic  feature  of 
the  disease.  The  clinical  features  of  the  glandular  enlargement 
(which  are  supposed  to  be  special  and  peculiar)  are  as  follows  : — 

In  the  first  place,  the  glandular  enlargement  is  not  a  mere  local 
condition,  but  is  more  or  less  widespread.  In  the  earlier  stages  of 
the  disease,  the  enlargement  may  for  a  time  be  limited,  or  may 
appear  to  be  limited,  to  one  group  of  glands  ;  but  in  well-marked 
and  typical  cases,  such  as  those  represented  in  my  Atlas  of  Clini- 
cal Medicine,  Plates  VIII.  and  IX.,  and  especially  in  the  advanced 
stages  of  the  disease,  all,  or  almost  all,  the  lymphatic  glands 
throughout  the  body  may  be  implicated. 

The  order  in  which  the  different  groups  of  lymphatic  glands 
are  involved  is,  according  to  Gowers,  as  follows  : — (1)  The  cervi- 
cal ;  (2)  the  axillary  ;  (3)  the  inguinal  ;  (4)  the  retro-peritoneal  ; 
(5)  the  bronchial  ;  (6)  the  mediastinal ;  and  (7)  the  mesenteric. 

In  some  cases,  enlarged  glands  may  be  felt  in  the  popliteal  space 
or  about  the  elbow ;  and  in  rare  cases,  adenoid  deposits  may 
develop  in  the  skin  or  subcutaneous  tissues.  In  a  remarkable  case 
which  came  under  my  notice  when  I  was  in  practice  in  North 
Shields,  all  the  glands  (external  and  internal)  throughout  the  body 
seemed  to  be  enlarged  ;  the  skin  was  thickly  studded  with  innumer- 
able nodules  of  lymphoid  tissue,  the  largest  of  which  were  the  size 
of  a  pea  ;  the  spleen  and  liver  were  much  enlarged  ;  and  both 
ovaries  were  transformed  into  large  round  tumours,  fully  the  size  of 
cricket  balls. 

In  the  second  place,  the  glandular  enlargement  is  painless,  non- 
suppurating,  and  non-caseating  in  character.  In  this  respect  it 
differs  from  a  simple  inflammation  or  a  typical  scrofulous  enlarge- 
ment of  the  glands. 


1 88  DISEASES   OF   THE   BLOOD   GLANDS. 

This  statement  does  not,  of  course,  imply  that  the  enlarged 
glands  in  Hodgkin's  disease  are  never  painful,  and  that  they  never 
suppurate  and  never  caseate.  In  exceptional  cases,  some  of  the 
enlarged  glands  may  be  painful  and  tender  to  the  touch  ;  in  fact, 
in  advanced  stages  of  the  disease  inflammation  of  the  capsule  of 
the  enlarged  glands  and  of  the  cellular  tissue  which  surrounds  the 
enlarged  glands  is  not  uncommon.  In  other  cases,  which  un- 
doubtedly seem  to  have  been  cases  of  Hodgkin's  disease,  one  or 
more  of  the  enlarged  glands  may  caseate  or  suppurate.  But  these 
conditions  (pain,  tenderness  on  pressure,  caseation,  and  suppuration) 
are  exceptional.  They  are  accidental  features.  They  are  in  no 
way  characteristic  of  the  disease ;  in  fact,  in  the  great  majority  of 
cases,  they  are  absent  altogether. 

It  may  perhaps  be  questioned  whether  some  of  the  cases  in 
which  suppuration  and  caseation  were  observed  were  true  examples 
of  the  disease.  Suppuration  and  caseation  appear  to  be  so  excep- 
tional, that  in  any  case  of  supposed  Hodgkin's  disease  in  which 
several  or  many  of  the  enlarged  glands  soften,  suppurate,  or  caseate, 
the  diagnosis  should  be  regarded  with  suspicion.  It  must,  however, 
be  admitted  that  suppuration  and  caseation  do  occasionally  occur. 
I  see  no  reason  why  a  gland  which  is  enlarged  by  Hodgkin's  disease 
may  not,  under  certain  conditions  (irritation,  defective  blood-supply, 
etc.),  suppurate  or  caseate  or  become  tubercular,  just  as  I  see  no 
reason  why  a  gland  or  group  of  glands  which  is  chronically  enlarged 
as  the  result  of  scrofula  may  not  become  implicated  in  the  general 
enlargement  of  Hodgkin's  disease.  But  suppuration  and  caseation 
in  Hodgkin's  disease  are  exceptional,  and  should  therefore  be 
regarded  as  accidental,  associated,  or  secondary  results. 

But,  notwithstanding  this  statement,  it  must  be  allowed  that 
cases  are  every  now  and  again  met  with  in  which  the  clinical 
symptoms,  the  nature  of  the  glandular  enlargement  and  the  course 
of  the  disease,  are  all  characteristic  of  Hodgkin's  disease,  and  in 
which  the  widespread  enlargement  of  the  lymphatic  glands  (pain- 
less and  non-suppurating)  is  found  on  post-mortem  examination  to 
be  undoubtedly  tubercular.     The  following  is  a  case  in  point  : — 

Case  of  Tubercular  Disease  of  the  Cervical,  Axillary,  Inguinal  and  Abdominal 
Glands,  with  Enlargement  of  the  Liver  and  Spleen,  resembling  Hodgkin's 
Disease. 

A.  B.,  aged  16,  a  scullery-maid,  was  admitted  to  Ward  27,  Edinburgh  Royal 

Infirmary,  on  15th   October  1893,  suffering  from  general  weakness  and 

glandular  enlargements  in  various  parts  of  the  body. 

Previous  History. — Some  of  the  cervical  glands  have  been  enlarged  as  long 

as  the  patient  can  remember  ;  they  never  gave  her  any  trouble  ;  they  never 


hodgkin's  disease.  189 

softened  nor  suppurated  ;  the  glandular  enlargements  have  never  been  painful. 
For  several  years  her  teeth  have  been  very  bad.  Her  general  health  was  very 
good  till  two  years  ago  ;  about  this  time  she  was  very  hard  worked  as  a  scullery- 
maid,  and  she  noticed  that  lumps  (enlarged  glands)  were  developing  in  both 
armpits  and  in  both  sides  of  the  neck.  For  the  past  year  she  has  been  getting 
thinner  and  weaker,  and  has  occasionally  suffered  from  diarrhoea. 

Family  History. — None  of  her  near  relatives  have,  so  far  as  she  knows, 
suffered  from  any  tubercular  affection  ;  her  parents,  brothers,  and  sisters  are 
strong  and  well. 

Condition  on  Admission. — The  patient  is  thin  and  anaemic  ;  the  feet  and 
face  are  slightly  swollen. 

Numerous  enlarged  lymphatic  glands  are  present  on  both  sides  of  the  neck 
from  the  chin  to  the  clavicle  and  behind  the  angles  of  the  jaw,  in  both  axillae 
and  in  both  groins.  The  enlarged  glands  are  hard  and  painless,  none  of 
them  present  the  slightest  indication  of  softening  or  suppuration.  The  enlarged 
glands  vary  in  size  from  a  hazel-nut  to  a  pigeon's  egg ;  with  few  exceptions 
they  are  isolated  and  freely  movable,  being  unadherent  either  to  one  another, 
to  the  skin,  or  the  surrounding  tissues.  On  the  right  side  of  the  neck  some  of 
the  enlarged  glands  are  adherent  and  matted  together.  The  skin  over  the 
enlarged  glands  is  quite  natural  in  appearance. 

The  abdomen  is  moderately  distended  ;  the  spleen  and  liver  both  appear 
to  be  enlarged  ;  a  mass  of  enlarged  glands  can  be  felt  in  the  centre  of  the 
abdominal  cavity  ;  there  is  some  fluid  in  the  peritoneal  cavity. 

The  temperature  is  above  the  normal — about  99°  in  the  morning  ;  1010,  1020 
in  the  evening.     The  skin  is  dry  and  harsh. 

The  patient  is  distinctly  anaemic  ;  the  red  corpuscles  number  3,320,000, 
and  the  haemoglobin  =  58  per  cent.;  the  polymorpho-nuclear  leucocytes  are  in 
slight  excess. 

There  is  some  impairment  of  the  percussion  note  in  the  right  infra-scapular 
region,  but  no  increase  of  vocal  resonance  and  no  moist  sounds.  There  is  no 
cough  or  expectoration. 

The  appetite  is  poor ;  the  patient  complains  of  thirst ;  the  bowels  are 
usually  moved  twice  daily  ;  there  have  been  several  attacks  of  diarrhoea. 

The  urine  contains  a  considerable  quantity  of  albumen  (equal  parts  of  serum 
albumen,  and  globulin),  no  blood,  some  casts. 

The  patient  has  never  menstruated. 

Diagnosis. — Hodgkin's  disease  and  nephritis,  probably  amyloid  degeneration 
of  the  kidneys  and  intestines. 

Treatment. — Arsenic,  Easton's  syrup,  quinine,  digitalis,  together  with 
nourishing  foods,  were  administered. 

Progress  of  the  Case. — There  was  no  improvement.  On  23rd  and  31st 
October  there  was  troublesome  diarrhoea.  On  6th  November  severe  vomiting 
and  collapse.     On  Qth  November  the  patient  died. 

Post-mortem  examination  made  by  Dr  Leith  on  10th  November. 

External  appearances. — Rigidity  and  lividity  present.  The  lymphatic  glands 
on  both  sides  of  the  neck,  in  both  axillae  and  in  both  groins,  are  enlarged,  form- 
ing firm  nodules.  The  glandular  masses  in  the  axillae  are  especially  large. 
The  individual  glands  are  not  greatly  enlarged.  On  section  the  enlarged  glands 
are  found  to  be  caseous,  almost  without  exception  ;  subsequent  microscopical 
examination  showed  that  they  were  all  tubercular.  The  left  lung  weighs  14  ozs.  ; 
a  depressed  scar  at  apex  passes  into  the  lung   tissue  in  the  form  of  fibrous 


190  DISEASES   OF   THE   BLOOD   GLANDS. 

pigmented  bands  ;  no  tubercles  can  be  seen  around  this  cicatrix,  but  it  is 
extremely  suspicious  of  a  tubercular  origin.  Over  the  whole  section  of  the  lung 
substance  a  few  small  firm  nodules,  apparently  of  recent  miliary  tubercle,  are 
scattered  ;  these  are  especially  frequent  in  the  deep  pleural  lymphatics.  The 
right  lung  weighs  14  oz. ;  it  shows  a  similar  scar  at  apex;  in  the  lung  tissue 
surrounding  it  there  are  several  caseous  areas,  evidently  tubercular;  and  over 
the  general  section  of  the  lung  there  are  scattered  tubercular  nodules  of  recent 
origin. 

The  heart  is  small,  but  quite  healthy. 

The  omentum  is  everywhere  adherent  to  the  pelvis  and  lateral  abdominal 
walls.  A  very  large  mass  of  enlarged  and  caseous  glands  is  present  in  the 
abdomen.  The  surface  of  the  intestine  is  covered  here  and  there  with  flaky- 
looking  organised  lymph  ;  the  coils  are  not  glued  together.  The  pelvic  con- 
tents are  quite  shut  off  from  the  abdomen  by  old  adhesions.  All  the  pelvic 
contents  are  much  matted  together.  The  left  ovary  is  fairly  free  and  healthy. 
The  right  ovary  is  surrounded  by  enlarged  and  indurated  glands. 

In  typical  cases,  and  in  the  earlier  .stages  of  the  disease,  at  all 
events,  the  enlarged  glands  preserve  their  individuality  of  contour ; 
they  are  not  matted  or  fused  together  and  adherent  as  scrofulous 
glands  usually  are.  The  individual  glands  can  be  felt  as  oval  or 
rounded  and  movable  nodules,  the  surface  of  which  is  smooth  and 
even.  The  skin  covering  the  enlarged  glands  is  neither  adherent 
nor  discoloured. 

The  degree  of  density  varies  in  different  cases,  and,  as  has  been 
already  stated  in  connection  with  the  morbid  anatomy,  two  varieties 
— a  hard  and  a  soft — have  been  described.  The  consistency  of  the 
enlarged  glands  seems  chiefly  to  depend  upon  the  amount  of  fibrous 
tissue  which  is  present.  In  some  cases,  the  enlarged  glands  feel  so 
soft  and  elastic  that  they  almost  appear  to  fluctuate;  in  others,  they 
feel  firm  and  solid  throughout,  but  even  in  these  (fibroid)  cases  they 
have  not  the  dense,  cartilaginous,  or  stony  hardness  which  cancerous 
glands  have.  In  the  earlier  stages  of  those  cases  in  which  the 
glandular  enlargements  are  rapidly  developed,  the  soft  form  of 
enlargement  is  apt  to  occur. 

The  size  of  the  individual  glands  varies  greatly  in  different 
cases  ;  the  individual  glands  may  attain  to  the  size  of  a  hen's  egg,  or 
even  larger  ;  while  the  glandular  masses,  as  a  whole,  may  be  as  large 
as  a  child's  head  (see  Atlas  of  Clinical  Medicine,  Plates  IX.  and  X.). 

In  the  advanced  stages  of  the  disease,  the  corresponding 
glandular  groups  on  the  opposite  sides  of  the  body  (two  sides  of 
the  neck,  two  axillae,  two  groins,  etc.)  are  usually  both  involved  ; 
but  the  enlargement  generally  begins  on  one  side  and  subsequently 
involves  the  other ;  it  rarely  happens  that  the  glandular  enlarge- 
ment is  so  equal  and  symmetrical  as  in  the  case  represented  in  my 
Atlas,  Plate  VIII. 


hodgkin's  disease.  191 

In  some  cases,  the  glandular  masses  in  the  neck,  axilla,  thorax, 
abdomen,  and  groin  are  all  joined  together  by  bands  of  enlarged 
glands. 

In  consequence  of  the  glandular  enlargement,  marked  deformity 
may  be  produced  (see  Atlas  of  Clinical  Medicine,  Plate  IX.) ;  and 
the  adjacent  parts  may  be  displaced  or  subjected  to  injurious 
pressure ;  the  enlarged  glands  in  the  neck  and  sub-maxillary 
regions  may  join,  and  encircle  the  greater  part  of  the  neck. 

The  symptoms  and  signs  which  may  be  produced  by  the 
pressure  of  the  enlarged  glands  are  multifarious  ;  the  more 
important  are  detailed  below. 

In  those  cases  in  which  the  enlarged  gland  itself  or  its  capsule 
becomes  inflamed,  or  in  which  the  capsule  becomes  perforated,  pain 
and  tenderness  on  pressure  may  be  complained  of,  and  the  struc- 
tures in  the  vicinity  of  the  affected  gland  may  become  involved  in 
the  inflammatory  process.  It  has  been  already  stated  that  under 
such  circumstances  suppuration  may  occur. 

Weakness,  Emaciation,  and  Cachexia. — Asthenia  is  one  of 
the  most  marked  features  of  the  disease.  Emaciation  is  often 
extreme,  more  especially  in  advanced  stages  of  the  case.  In  acute 
cases  (i.e.,  cases  in  which  the  glandular  enlargement  is  rapidly 
developed)  and  in  the  later  stages  of  many  of  the  more  chronic 
cases,  a  marked  condition  of  cachexia  is  often  developed. 

The  weakness  and  cachexia  are,  as  a  rule,  developed  gradually, 
and  are,  in  my  experience,  usually  proportionate  to  the  extent  and 
degree  of  the  glandular  enlargement. 

So  long  as  the  glandular  enlargement  is  localised,  so  long,  more 
especially,  as  one  or  two  groups  of  the  external  glands  are  alone 
affected,  there  may  be  little  or  no  emaciation — in  short,  little  or  no 
constitutional  disturbance. 

In  those  cases,  on  the  other  hand,  in  which  the  glandular 
enlargement  is  widespread,  in  which  the  internal  glands  are  in- 
volved, in  which  the  spleen  and  the  glandular  structures  in  the 
intestine  are  affected,  in  which  the  disease  is  quickly  and  actively 
progressing,  in  which  the  febrile  disturbance  is  considerable,  and  in 
which  inflammatory  complications  such  as  empyema  are  present, 
the  emaciation  may  be  very  great  indeed.  In  at  least  three  cases 
of  Hodgkin's  disease,  I  have  seen  the  glutei  muscles  almost  com- 
pletely atrophied,  and  the  pelvic  bones  laid  bare,  as  it  were,  by  the 
emaciation.  Such  a  condition  is  of  very  serious  significance  ;  for 
in  my  experience,  marked  wasting  of  the  glutei  muscles  is  rarely,  if 
ever,  produced  unless  the  emaciation  of  which  it  is  part  and  parcel 
is  extreme.     A  high  degree  of  atrophy  of  the  glutei  muscles  and  of 


192  DISEASES   OF   THE   BLOOD   GLANDS. 

the  thick  cushion  of  fat  which  normally  overlies  the  buttocks  is 
indicative  of  a  very  profound  disturbance  of  nutrition. 

Anaemia  and  the  condition  of  the  blood. — In  well-marked 
cases  of  Hodgkin's  disease,  the  skin  and  mucous  membranes  are 
usually  pale,  and  the  red  blood  corpuscles  are  diminished  in 
numbers.  Some  writers,  indeed,  state  that  anaemia  is  always 
present  when  the  glandular  enlargement  is  widespread  and  well 
marked  ;  but  with  this  statement  I  am  unable  to  agree.  I  have 
myself  met  with  two  well-marked  cases  of  the  disease  in  which  the 
red  blood  corpuscles  were  respectively  5,390,000  and  4,550,000  per 
cubic  millimetre.  In  the  case  represented  in  my  Atlas  of  Clinical 
Medicine  (Plate  VIII.),  Dr  Handford  found  that  the  red  blood 
corpuscles  numbered  4,807,000,  and  seven  weeks  later  4,895,000, 
per  cubic  millimetre.  In  a  case  reported  by  Osier,  in  which  the 
cervical  and  axillary  glands  were  enormously  enlarged,  the  red 
blood  corpuscles  numbered  4,250,000  per  cubic  millimetre,  and  did 
not  undergo  any  diminution  in  numbers  during  the  three  weeks 
that  the  patient  was  under  observation  in  hospital.  In  the  case 
which  is  represented  in  my  Atlas  (Plate  IX.),  the  red  corpuscles, 
which  in  December  1886  numbered  2,930,000,  had  increased  in 
February  1887  to  4,180,000  per  cubic  millimetre. 

It  is  impossible  to  suppose  that  in  all  of  these  cases,  in  which 
the  observations  were  made  by  four  independent  observers,  the 
results  were  erroneous.  It  must,  I  think,  be  allowed  (if  it  be 
granted  that  in  these  cases  the  glandular  enlargement  was  due  to 
Hodgkin's  disease  and  not  to  tubercle)  that,  in  certain  stages  of 
the  disease,  the  red  corpuscles  are  not  diminished,  or  are  only  very 
slightly  diminished,  in  numbers.  But  this  is  exceptional.  In  most 
cases  of  Hodgkin's  disease  anaemia  is  present  ;  and  it  is  probably 
correct  to  say  that  in  all  well-marked  cases  of  the  disease  the  red 
blood  corpuscles  are  diminished  in  numbers  {i.e.,  there  is  more  or 
less  anaemia)  at  some  period  or  other  of  their  course. 

The  degree  of  anaemia  varies  in  different  cases.  Gowers  states 
that  anaemia  is  one  of  the  most  conspicuous  features  of  the  disease  ; 
he  found  the  red  corpuscles  reduced  to  sixty  per  cent,  of  the 
normal,  in  some  patients  affected  with  the  disease  in  whom  the  face 
was  well  coloured. 

The  red  corpuscles  are  usually  normal  as  regards  their  size  and 
shape,  but  in  some  cases  a  number  of  small  (imperfectly  developed) 
red  corpuscles  are  present ;  in  other  cases,  more  especially,  I  think, 
in  those  cases  in  which  the  anaemia  is  well  marked,  the  red  cor- 
puscles do  not  form  rouleaux  in  the  normal  manner.  Poikilocytosis 
is  in  my  experience  rarely  present,   at  all  events  in  any  marked 


hodgkin's  disease.  193 

degree ;  but   the  statements  of  different  observers  differ  on    this 
point. 

The  condition  of  the  white  blood  corpuscles  is  variable.  In 
most  of  the  cases  which  have  come  under  my  own  notice,  the  white 
corpuscles  have  been  slightly  increased  in  numbers,  and  for  the 
most  part  of  small  size  ;  but  an  excess  of  white  corpuscles  appears 
to  be  exceptional,  for  Gowers  states  :  "  In  the  majority  of  cases 
there  is  no  excess  of  white  corpuscles  in  the  blood.  In  a  minority 
of  cases,  there  is  an  excess,  slight  or  considerable.  Out  of  sixty- 
four  cases  in  which  the  blood  was  examined  by  the  microscope, 
there  was  no  excess  of  white  corpuscles  in  thirty-nine.  In  the 
remaining  twenty-five  cases,  there  was  an  excess,  which  in  nineteen 
was  moderate,  in  three  was  slight.  In  three  others,  there  was  no 
excess  of  leucocytes  during  the  early  period  of  the  case,  but  a  slight 
excess  was  present  during  its  later  stages."  *  Trousseau,  in  his 
well-known  lecture  on  the  subject,  also  says :  "  Gentlemen,  I 
cannot  tell  you  what  special  action  in  the  composition  of  the  blood 
is  caused  by  general  hypertrophy  of  the  glands  ;  I  do  not  know 
whether  it  notably  diminishes  the  leucocytes,  but  I  am  certain  that 
it  does  not  increase  them."  f 

In  exceptional  cases,  the  white  blood  corpuscles  are  in  consider- 
able excess  ;  this  is  especially  apt  to  occur  in  the  later  stages  of 
the  disease.  Many  writers  speak  of  cases  of  this  kind  as  a  com- 
bination of  Hodgkin's  disease,  and  of  lymphatic  leucocythsemia ; 
but  the  correctness  of  this  view  is,  I  think,  very  questionable  ;  in 
many  cases  of  this  kind,  the  increase  of  the  white  corpuscles  appears 
to  be  the  result  of  a  terminal  leucocytosis,  and  in  no  way  indicative 
of  lymphatic  leucocythsemia. 

Dr  Robert  Muir  informs  me  that  in  the  only  typical  case  of 
lymphadenoma  (with  characteristic  lesions  in  the  spleen,  etc.)  which 
he  has  examined  post  mortem,  "  the  leucocytes  were  between 
20,000  and  30,000  per  c.mm.,  and  the  proportion  of  polymorpho- 
nuclear leucocytes  are  very  much  increased — a  true  leucocytosis." 
He  adds  :  "  In  two  cases,  in  which  the  blood  was  examined  during 
life,  I  found  a  slight  excess  of  lymphocytes — they  were  both  young 
subjects — and  I  have  noticed  that  in  early  life  the  proportion  of 
lymphocytes  tends  to  be  raised  more  readily  than  in  adults.  I 
should  say  that  in  lymphadenoma  the  increase  of  leucocytes  is 
never  very  great ;  sometimes  there  is  an  excess  of  lymphocytes, 
sometimes  an  ordinary  leucocytosis." 

*  Russell  Reynolds'  System  of  Medicine,  vol.  v.,  p.  334. 
t  Sydenham  Society  Translation,  vol.  v.,  p.  201. 
N 


194  DISEASES   OF    THE   BLOOD   GLANDS. 

Cabot  sums  up  the  characters  of  the  blood  in  Hodgkin's  disease 
as  follows  : — 

"  Normal  blood  in  early  stages. 

"  Later  often  marked  anaemia. 

"  Sometimes  leucocytosis."  * 

In  those  cases  of  Hodgkin's  disease  in  which  the  anaemia  is 
marked,  shortness  of  breath,  palpitation,  and  the  other  well-known 
symptoms  associated  with  a  deficiency  of  the  red  blood  corpuscles 
(oxygen  -  carriers),  may,  of  course,  be  present;  but  Hodgkin's 
disease,  or  lymphatic  anaemia,  as  Sir  Samuel  Wilks  has  termed  it, 
differs  from  other  forms  of  anaemia  (chlorosis  and  progressive 
pernicious  anaemia,  for  example)  in  the  fact  that  the  patients 
affected  by  it  are  usually  emaciated  as  well  as  anaemic. 

The  Condition  of  the  Heart  and  Pulse. — The  action  of  the 
heart  is  usually  quick  and  feeble,  and  in  many  cases  the  organ  is 
found  to  be  more  or  less  atrophied  after  death. 

The  pulse  is  usually  quick,  small,  and  weak  ;  in  some  cases 
it  is  markedly  dicrotic,  more  particularly  in  the  advanced  stages 
of  the  disease,  and  in  those  cases  in  which  the  pyrexia  is  consider- 
able. 

CEdema  of  the  feet  is  of  frequent  occurrence  in  the  later  stages 
of  the  disease ;  in  some  cases,  it  is  merely  the  result  of  anaemia, 
debility,  or  cachexia  ;  in  others,  it  is  due  to  the  pressure  of  the 
enlarged  glands  upon  the  iliac  or  femoral  veins,  or  the  inferior  vena 
cava. 

Haemorrhages. — Epistaxis  occurs  in  some  cases ;  purpuric 
eruptions,  and  unhealthy  inflammations  of  the  skin  or  other  parts 
(erysipelas,  boils,  stomatitis,  etc.),  may  develop  in  those  cases  in 
which  the  anaemia  and  cachexia  are  great. 

Loss  of  Appetite,  Dyspepsia,  and  other  Symptoms  indi- 
cative of  Derangement  of  the  Gastro-Intestinal  Functions. — 
In  well-marked  cases  of  Hodgkin's  disease,  the  appetite  is  usually 
much  impaired  or  entirely  lost ;  and  dyspepsia,  vomiting,  and 
diarrhoea  are  of  frequent  occurrence.  In  some  cases,  these  symptoms 
are  merely  the  result  of  the  anaemia,  debility,  and  cachexia  ;  in 
others,  they  are  associated  with  deposits  of  lymphoid  tissue,  or  the 
presence  of  ulcerations,  in  the  stomach  or  intestine. 

Difficult)'  in  swallowing  is  in  some  cases  due  to  the  pressure  of 
enlarged  glands  upon  the  oesophagus. 

Pyrexia. — In  several  of  the  cases  of  Hodgkin's  disease  which 
have  come  under  my  own  observation  (it  would  perhaps  be  more 

*  "Clinical  Examination  of  the  Blood,"  p.  157. 


HODGKIN'S   DISEASE.  195 

correct  to  say  which  were  diagnosed  as  cases  of  Hodgkin's  disease), 
there  has  been  little  or  no  febrile  disturbance  ;  but  elevation  of 
temperature  is  of  frequent  occurrence  during  the  course  of  the 
disease. 

The  degree  of  fever  is  not  usually  great  (1010,  1020,  or  1030  F.), 
but  temperatures  of  1040  and  1050  F.  are  occasionally  met  with. 

Gowers  describes  three  types  of  fever  in  Hodgkin's  disease.  "In 
one  the  temperature  is  continuously  raised,  presenting  very  slight 
diurnal  variations  of  a  degree  or  a  degree  and  a  half.  The  highest 
temperature  is  sometimes  in  the  morning,  sometimes  in  the  evening. 
Occasionally  the  temperature  may  descend  to  the  normal  and  rise 
again.  The  degree  of  elevation  is  usually  from  ioo°  to  103°.  A 
second  type  is  characterised  by  periods  of  pyrexia,  in  which  for 
several  days  a  high  temperature  is  maintained,  the  daily  variation 
being  slight.  Alternating  with  these  pyrexial  periods  are  intervals 
of  several  days  in  which  the  temperature  is  normal,  or  nearly  so. 
The  height  attained  by  the  fever  may  be  considerable,  sometimes 
reaching  1050,  as  in  the  case  from  which  a  chart  is  given.  A  third 
type  is  characterised  by  morning  remissions,  the  temperature  being 
always  higher  in  the  evening  than  in  the  morning.  The  daily 
variations  are  from  one  to  three  degrees,  the  morning  temperature 
being  at  or  below  ioo°,  sometimes  normal,  and  the  evening 
temperature  being  from  ioi°  to  103V  * 

Fever  is  most  apt  to  occur  in  acute  cases,  in  young  subjects, 
and  in  those  cases  in  which  inflammatory  complications,  such  as 
broncho-pneumonia,  empyema,  etc.,  are  developed.  In  some  of  the 
cases  in  which  fever  is  prominent,  the  glandular  enlargement  is 
undoubtedly  tubercular. 

Enlargement  of  the  Spleen. — This  occurs  in  the  majority  of 
cases  of  the  disease.  The  degree  of  enlargement  is  not,  as  a 
rule,  great,  but  sometimes  (as  in  the  case  represented  in  my 
Atlas  of  Clinical  Medicine,  Plate  VIII.)  it  is  very  considerable. 
The  surface  of  the  enlarged  spleen  is  usually  smooth  ;  in  rare  in- 
stances it  may  be  nodulated.  Perisplenitis,  with  thickening  of  the 
capsule,  and  perhaps  the  formation  of  adhesions  to  the  surrounding 
parts,  is  not  uncommon  in  the  later  stages  of  the  disease.  In  those 
cases  in  which  perisplenitis  is  present,  pain  and  tenderness  on 
pressure  over  the  enlarged  organs  may  be  complained  of. 

The  enlargement  of  the  spleen  may  be  due  either  to  the  pre- 
sence of  disseminated  lymphoid  nodules  or  an  increase  (hypertrophy) 
of  the  splenic  tissue.     In  many  cases  both  of  these  conditions  are 

*  Russell  Reynolds'  System  of  Medicine,  vol.  v.,  p.  336. 


196  DISEASES   OF   THE   BLOOD   GLANDS. 

present.  The  presence  of  nodules  of  lymphoid  tissue  in  the  spleen 
is  seldom  per  se  {i.e.,  in  the  absence  of  hypertrophy)  the  cause  of 
marked  enlargement  of  the  organ.  In  short,  in  the  great  majority 
of  cases  of  Hodgkin's  disease  the  enlargement  of  the  spleen,  though 
in  many  cases  it  is  sufficient  to  enable  one  to  detect  it  by  palpation, 
is  not  great 

Enlargement  of  the  Tonsils,  Liver,  and  other  organs. — 
Enlargement  of  the  tonsils  occasionally  occurs  ;  when  considerable, 
and  especially  if  associated  with  great  swelling  of  the  cervical 
glands,  and  the  presence  of  lymphoid  deposits  in  the  pharnyx  and 
adjacent  parts,  it  may  be  attended  with  alterations  in  voice, 
deafness,  difficulty  in  swallowing,  and  shortness  of  breath.  The 
enlarged  tonsils  may  ulcerate,  and  in  rare  cases — one  has  come 
under  my  notice — may  be  the  seat  of  diphtheritic  deposits. 

Enlargement  of  the  liver,  sufficiently  great  to  be  detected  during 
life,  is  present  in  a  certain  number  of  cases  ;  in  a  few  cases  the 
enlargement  is  great. 

The  testicle  is  occasionally  the  seat  of  lymphoid  deposits.  In  a 
remarkable  case  which,  through  the  kindness  of  Mr  Alexis  Thom- 
son, I  was  able  to  record  and  figure  in  my  Atlas  (see  Plate  X),  the 
mammce  were  enormously  enlarged.  The  thymus  gland,  suprarenal 
capsules,  kidneys,  and  ovaj'ies  are  in  some  cases  affected,  but  it  is 
seldom  that  the  enlargement  of  these  organs  (the  thymus,  perhaps, 
most  frequently  excepted)  is  sufficient  to  enable  one  to  detect  it 
during  life.  In  the  North  Shields  case  to  which  I  have  already 
referred,  the  enlarged  ovaries  could,  however,  be  very  distinctly 
felt  in  the  abdomen ;  they  were  as  large  as  cricket  balls. 

In  some  cases  in  which  the  marrow  of  the  bones  is  more 
markedly  affected  than  it  is  in  the  great  majority  of  cases  of 
Hodgkin's  disease,  some  of  the  bones  (sternum,  tibiae,  etc.)  may  be 
painful  and,  perhaps,  in  places  distinctly  swollen. 

Symptoms  and  signs  due  to  the  pressure  of  the  enlarged 
lymphatic  glands  upon  adjacent  structures  and  parts. — The 
"pressure-symptoms  and  signs"  which  may  be  present  in  Hodgkin's 
disease  are  very  numerous  ;  in  some  cases,  as  for  instance  in  those 
cases  in  which  the  internal  glands  are  chiefly  affected,  they  may  be 
the  most  striking  clinical  features  of  the  case. 

The  enlarged  cervical  glands  may  displace  or  compress  the 
trachea,  the  oesophagus,  or  the  nerves,  veins,  and  arteries  in  the  neck. 
Difficulty  in  breathing,  alterations  in  voice,  cough,  difficulty  in 
swallowing,  inequality  in  the  size  of  the  pupils,  vomiting,  irregu- 
larity of  the  action  of  the  heart,  swelling  of  the  head  and  face,  and 
various  cerebral  symptoms  due  to  impeded  venous  circulation  or 


HODGKIN  S   DISEASE.  197 

defective  arterial  supply  to  the  brain  (such  as  mental  obfuscation, 
giddiness,  convulsions,  coma)  may  result. 

The  enlarged  glands  within  the  cavity  of  the  thorax  (the 
bronchial  and  mediastinal  glands,  and  the  enlarged  thymus)  may 
displace  or  compress  the  root  of  the  lung,  the  bronchi,  the  trachea, 
the  oesophagus,  the  recurrent  laryngeal  nerve,  the  superior  vena 
cava,  the  aorta  and  its  branches,  the  pulmonary  artery,  and  even 
the  heart  itself.  Difficulty  in  breathing,  cough,  alterations  in  voice, 
stridor,  difficulty  in  swallowing,  oedema  of  the  head  and  neck, 
paralysis  of  the  left  vocal  cord,  inequality  in  the  size  of  the  pupils, 
murmurs  due  to  displacement  of  the  heart  or  compression  of  the 
great  vessels,  displacement  of  the  apex-beat,  extensive  dulness  on 
percussion — in  short,  all  the  symptoms  and  signs  which  may  be 
present  in  cases  of  solid  intra-thoracic  tumour — may  result. 

The  enlarged  glands  in  the  cavities  of  the  abdomen  and  pelvis 
may  compress  the  lumbar,  sacral,  or  solar  plexuses,  the  stomach, 
portal  vein,  inferior  vena  cava,  etc.,  and  may  produce  a  great 
variety  of  symptoms,  such  as  cedema  of  the  feet,  ascites,  jaundice, 
vomiting,  shooting  pains  in  the  lower  extremities,  paralysis  of  the 
lower  limbs,  etc. 

The  enlarged  glands  in  the  axillo3  and  groins  may  interfere  with 
the  free  movement  of  the  upper  or  lower  limbs,  and  may  press 
upon  the  nerves,  veins,  and  arteries  in  their  neighbourhood  ;  pains 
in  the  limbs,  paralysis,  and  cedema  may  result. 

The  pressure  of  lymphoid  deposits  on  the  spinal  cord  may 
produce  paraplegia.     Osier  has  recorded  a  case  in  point. 

Symptoms  due  to  inflammatory  complications  in  the  neigh- 
bourhood of  the  enlarged  glands  and  associated  lesions. — As 
I  have  already  stated,  inflammation  of  the  capsule  of  the  enlarged 
glands  (periadenitis)  not  unfrequently  occurs  ;  pain  and  tenderness 
on  pressure,  with  matting  together  (fusion,  as  it  were)  of  the  indi- 
vidual glandular  masses  may  in  consequence  be  developed. 

In  some  cases,  the  adjacent  structures  become  implicated  in 
the  inflammatory  process  ;  adhesion  of  the  glandular  masses  to  the 
skin,  and,  in  rare  cases,  ulceration  of  the  skin  overlying  the 
enlarged  glands,  may  result.  The  question  arises  whether  in  these 
cases  the  glandular  enlargement  is  tubercular  or  due  to  Hodgkin's 
disease. 

In  exceptional  cases,  the  enlarged  glands  themselves  suppurate 
or  caseate.  The  suppuration  is,  so  far  as  I  know,  always  local,  i.e., 
confined  to  a  limited  number  of  the  enlarged  glands.  I  am  not  ac- 
quainted with  any  case  of  Hodgkin's  disease  in  which  all  the  enlarged 
glands,  or  many  of  them,  in  different  parts  of  the  body,  have  softened 


I98  DISEASES   OF    THE   BLOOD   GLANDS. 

and  suppurated  ;  though  widespread  caseation  without  suppura- 
tion is,  in  some  cases,  which  during  life  appeared  to  be  cases  of 
Hodgkin's  disease,  found  after  death.  I  have  already  detailed  a 
case  in  point.  In  any  case  of  supposed  Hodgkin's  disease  in 
which  widespread  suppuration  or  caseation  were  present  and 
obvious  during  life,  I  should  be  disposed  to  doubt  the  correctness 
of  the  diagnosis,  and  to  suppose  that  the  primary  glandular  en- 
largement (on  the  top  of  which,  so  to  speak,  the  suppuration  or 
caseation  was  developed)  was  due  to  some  pathological  condition 
other  than  Hodgkin's  disease,  e.g.,  to  tubercle. 

It  is  not  unlikely  that  in  some  cases  of  Hodgkin's  disease  in 
which  one  or  more  of  the  enlarged  glands  suppurate  or  caseate, 
they  were,  previous  to  the  development  of  the  Hodgkin's  disease, 
the  seat  of  an  inflammatory  or  scrofulous  lesion.  Again,  as  I  have 
already  pointed  out,  I  see  no  a  priori  reason  why  tubercle  should 
not  be  engrafted  upon  Hodgkin's  disease. 

Thrombosis  of  the  veins  which  are  embedded  in,  and  com- 
pressed by,  the  enlarged  glands  is  developed  in  some  cases. 
Complete  venous  obstruction  produced  in  this  manner  is  usually 
attended  with  great  oedema  in  the  area  from  which  the  obstructed 
vein  draws  its  blood  supply.  Effusion  into  the  pleural,  pericardial, 
or  peritoneal  cavities  is  sometimes  produced  in  this  manner.  In 
some  cases,  pleurisy,  empyema,  pericarditis,  and  peritonitis,  which 
is  usually  localised,  are  developed.  As  has  been  already  stated, 
stomatitis,  diphtheria,  and  erysipelas  occasionally  occur. 

The  condition  of  the  respiratory  apparatus. — In  addition 
to  the  disturbances  of  the  respiratory  apparatus  which  have  been 
already  mentioned,  lung  complications,  such  as  bronchitis,  broncho- 
pneumonia, and  less  frequently  croupous  pneumonia,  which  is 
usually  localised,  are  of  frequent  occurrence.  A  low  form  of 
chronic  inflammation  of  the  pulmonary  tissue,  probably  due  to 
compression  of  the  vascular  and  nervous  structures  in  the  root  of 
the  lung,  is  occasionally  developed  in  those  cases  in  which  the 
bronchial  and  mediastinal  glands  are  implicated. 

The  condition  of  the  urine. — The  kidneys  are  sometimes  the 
seat  of  inflammatory  or  degenerative  changes  ;  the  characteristic 
symptoms  and  signs  of  Bright's  disease  (general  dropsy,  albu- 
minuria, tube  casts  in  the  urine)  may,  of  course,  be  developed  in 
such  cases. 

Nervous  Symptoms. — Drowsiness,  mental  apathy,  coma,  or 
convulsions  occasionally  occur  in  the  later  stages  of  the  disease. 
These  symptoms  are  not  usually  indicative  of  an)-  actual  lesion 
(such  as  lymphoid  deposits)  in  the  brain  tissue,  but  are  rather  the 


hodgkin's  disease.  199 

result  of  the  anaemic  and  cachectic  condition,  alterations  in  the 
venous  or  arterial  blood  supply  of  the  nervous  tissues,  and  the 
defective  nutrition  which  results  therefrom. 

Clinical  Types,  Duration  and  Course. 

From  the  description  which  has  just  been  given,  it  will  be 
apparent  that  different  cases  of  Hodgkin's  disease  present  differ- 
ences in  respect  to  their  symptoms.  When  we  study  the  manner 
in  which  the  chief  symptoms — the  glandular  enlargements  and  the 
local  symptoms  which  result  therefrom,  on  the  one  hand,  and  the 
constitutional  symptoms  (debility,  emaciation,  anaemia,  cachexia, 
fever,  etc.),  on  the  other — are  grouped  together  ;  the  order  in  which 
the  symptoms  are  developed  ;  and  the  rapidity  with  which  the 
disease  progresses,  it  is  possible  to  arrange  different  cases  of 
Hodgkin's  disease  into  certain  clinical  groups.  It  must,  however, 
be  distinctly  understood  that  the  division  is  a  rough  one,  and,  so 
far  as  our  present  knowledge  enables  us  to  judge,  artificial,  and  that 
the  different  groups  or  types  run  insensibly  one  into  the  other. 
Nevertheless,  some  such  classification  as  that  which  is  adopted 
below  is  of  use  to  the  practical  physician,  chiefly  for  the  purposes 
of  prognosis. 

In  most  cases,  the  disease  develops  gradually  and  runs  a  slow 
and  chronic  course,  the  duration  (dating  the  commencement  from 
the  period  at  which  the  glandular  affection  is  first  observed)  being, 
in  the  majority  of  cases,  at  least  eighteen  months,  and  in  some  cases 
considerably  longer. 

In  a  minority  of  cases,  the  progress  of  the  disease  is  much  more 
rapid,  the  fatal  termination  being  reached  within  a  few  weeks  or 
months  from  the  period  at  which  the  symptoms  were  first  noticed. 

These  two  groups  {i.e.,  cases  of  Hodgkin's  disease  which  run  a 
chronic  or  protracted  course,  and  cases  of  Hodgkin's  disease  which 
run  a  rapid  or  acute  course)  are  not  sharply  defined  ;  they  are  con- 
nected by  cases  having  an  intermediate  duration.  But  it  is  often 
possible,  when  the  patient  first  comes  under  observation,  to  predict 
with  tolerable  accuracy  whether  the  case  is  likely  to  run  a  rapid  or 
a  protracted  course.  Hence  this  division  into  acute  and  chronic, 
though  not,  so  far  as  our  present  knowledge  enables  us  to  judge, 
founded  upon  any  distinct  etiological  or  pathological  differences,  is 
of  practical  use  for  the  purposes  of  prognosis. 

In  most  cases  of  Hodgkin's  disease,  the  constitutional  symptoms 
are  developed  later  than,  and  are  apparently  the  result  of,  the 
glandular  enlargements.  This  statement  chiefly  applies  to  the 
more  common  (chronic)  form  of  the  disease. 


200  DISEASES   OF   THE   BLOOD   GLANDS. 

Some  authorities  divide  the  disease  into  three  stages,  viz. : — first, 
a  stage  of  localised  glandular  enlargement ;  second,  a  stage  of  gene- 
ralised glandular  enlargement  ;  and  third,  a  stage  of  anaemia, 
cachexia,  and  profound  constitutional  disturbance.  Trousseau 
terms  these  three  periods,  the  latent  period,  the  period  of  progress 
and  generalisation,  and  the  cachectic  period. 

In  many  cases,  these  three  stages  can  undoubtedly  be  observed. 
But  as  I  shall  presently  point  out,  in  speaking  of  the  diagnosis,  so 
long  as  the  glandular  enlargement  is  merely  local,  and  there  are 
no  constitutional  symptoms,  although  the  presence  of  the  disease 
may  be  suspected,  it  cannot  be  positively  diagnosed.  It  is  only  when 
the  glandular  enlargement  has  become  generalised  that  Hodgkin's 
disease  can  with  any  degree  of  certainty  be  recognised,  and  even 
then  it  is  often  difficult,  as  I  have  more  than  once  pointed  out,  to 
exclude  tubercle. 

Again,  in  some  cases  the  stage  of  local  enlargement  is  wanting, 
or  at  all  events  appears  to  be  wanting ;  and  the  several  groups  of 
glands  in  different  parts  of  the  body  appear  to  be  simultaneously, 
or  to  all  intents  and  purposes  simultaneously,  affected.  It  is  pro- 
bable that  in  many  of  these  cases  the  generalised  enlargement  was 
preceded  by  a  local  enlargement  of  some  of  the  external  glands 
which  had  escaped  notice,  or  by  an  enlargement  of  some  of  the 
internal  glands  which  could  not  be  detected. 

In  another  group  of  cases,  the  constitutional  symptoms  are 
developed,  or  appear  to  be  developed,  simultaneously  with  the 
glandular  enlargement. 

In  still  another  group,  the  constitutional  symptoms  are  deve- 
loped, or  appear  to  be  developed,  before  (prior  to)  the  glandular 
enlargements. 

It  is  probable  that  in  many  of  the  cases  which  are  included  in 
the  last  two  groups,  enlargement  of  the  internal  glands  does  actually 
precede  the  development  of  the  constitutional  symptoms.  Cases  in 
which  this  occurs  are  not  in  reality  exceptional ;  clinically  they 
appear  to  be  exceptional,  but  pathologically  and  as  a  matter  of  fact 
they  conform  to  the  general  rule,  viz.,  that  the  constitutional  symp- 
toms follow  the  glandular  enlargement. 

In  another  group,  the  internal  glands  (the  bronchial  and  medi- 
astinal glands,  and  the  thymus,  for  instance)  are  alone  affected.  It 
is  probable  that  in  some  of  these  cases  the  glandular  enlargement 
is  not  in  reality  due  to  Hodgkin's  disease  ;  but  it  is  nevertheless 
true  that  our  present  methods  of  pathological  research  do  not 
enable  us  to  differentiate  them. 

It  may  be  stated,  as  a  general  rule,  that  those  cases  run  a  rapid 


HODGKIN  S   DISEASE.  201 

course  in  which  cachexia  and  constitutional  symptoms  are  deve- 
loped early,  in  which  several  groups  of  glands  are  simultaneously, 
or  apparently  simultaneously,  affected,*  and  in  which  the  glandular 
enlargement  is  rapidly  developed.  The  cases  analysed  by  Gowers 
seem  to  show  that  after  the  age  of  50,  and  still  more  after  the  age 
of  60,  the  course  of  the  disease  is  usually  rapid  ;  but  further  obser- 
vation is  probably  required  before  this  conclusion  can  be  finally 
accepted. 

Mode  of  Death. — Gradual  failure  of  the  vital  powers,  the  result 
of  the  progressive  asthenia  and  cachexia,  is  the  most  frequent  mode 
of  death  ;  in  some  cases,  the  fatal  termination  is  due  to  asphyxia, 
the  result  of  the  pressure  of  the  enlarged  glands  upon  the  trachea, 
larynx,  or  bronchi ;  in  many  cases,  the  immediate  cause  of  death  is 
the  development  of  some  intercurrent  illness  or  complication,  such 
as  pneumonia,  pleurisy,  pericarditis,  diphtheria,  etc.  Epistaxis  and 
diarrhoea,  in  some  cases,  precede  and  hasten  the  fatal  issue. 

Diagnosis. 

In  typical  and  advanced  cases  of  the  disease,  the  diagnosis  does 
not  as  a  rule  present  any  great  difficulty.  The  peculiar  characters 
of  the  glandular  enlargement,  more  especially  the  absence  of  casea- 
tion and  suppuration,  and  the  fact  that  the  enlarged  glands  have 
not  the  cartilaginous  and  stony  hardness  of  cancer  ;  the  fact  that 
the  glandular  enlargement  is  not  merely  local,  but  that  different 
groups  of  glands  throughout  the  body  (groups  of  glands  which  are 
not,  as  it  were,  in  direct  anatomical  continuity)  are  affected  ;  the 
absence  of  any  primary,  local,  malignant  lesion,  such  as  cancer  of 
the  mamma,  stomach,  or  other  internal  organ  ;  the  presence  of 
enlargement  of  the  spleen,  without,  in  many  cases,  any  marked 
increase  in  the  number  of  the  white  blood  corpuscles  ;  the  presence 
of  lymphoid  deposits  in  the  tonsils  or  (but  this  is  rare)  in  the  skin  ; 
the  presence  of  enlargement  of  the  liver,  thymus  gland,  etc.  (sug- 
gestive of  lymphoid  deposits  in  these  organs) ;  and  the  presence  of 
the  characteristic  constitutional  symptoms  (asthenia,  anaemia, 
emaciation,  cachexia,  etc.),  usually  enable  us  to  distinguish  the 
disease  from  the  other  conditions  with  which  it  is  likely  to  be 
confounded. 

But  even  these  characteristics  are  not  absolutely  conclusive  ; 
for  it  cannot  be  too  frequently  repeated  that  in  some  cases  in  which 

*  Wunderlich's  opinion  was  different  on  this  point.  He  thought  that  in 
those  cases  in  which  several  groups  of  glands  were  simultaneously  affected,  the 
disease  was  apt  to  develop  slowly. 


202  DISEASES   OE   THE   BLOOD   GLANDS. 

the  clinical  symptoms  and  the  character  of  the  glandular  enlarge- 
ment are  typical  of  Hodgkin's  disease,  the  enlarged  glands  are 
found  on  post-mortem  examination  to  be  the  seat  of  a  widespread 
tubercular  lesion.  I  have  already  expressed  the  opinion  that  these 
cases  are  probably  much  more  common  than  is  usually  supposed. 

In  the  earlier  stages  of  the  disease,  the  diagnosis  is  very  difficult 
and  often  impossible ;  in  some  cases,  for  example,  in  which  the 
cervical  and  axillary  glands  are  enlarged,  hard,  painless  and  non- 
suppurating,  and  in  which  there  are  no  constitutional  symptoms,  it 
is  extremely  difficult  to  come  to  a  conclusion  as  to  the  exact  nature 
of1  the  glandular  enlargement,  more  especially  in  which  the 
glandular  enlargement  is  of  long  duration.  Several  cases  of  this 
kind  have  come  under  my  own  notice. 

Hodgkin's  disease  has  to  be  differentiated  from  the  other  affec- 
tions in  which  the  enlargement  of  the  lymphatic  glands  occurs, 
and  especially  from  local  lymphatic  overgrowth  (simple  or  local 
lymphoma),  from  scrofulous  enlargement,  and  from  cancer  and 
sarcoma  (true  malignant  disease)  of  the  lymphatic  glands.  In 
some  cases,  the  differential  diagnosis  is  difficult,  if  not  impossible. 
The  chief  points  of  distinction  are  as  follows  : — 

The  differential  diagnosis  of  Hodgkin's  disease  and  of 
local  lymphatic  overgrowth  (simple,  or  local,  non-malignant 
lymphoma). —  In  fully-developed  cases  of  Hodgkin's  disease  — 
cases  in  which  the  lymphatic  enlargements  are  generalised  and 
the  characteristic  constitutional  symptoms  (asthenia,  anaemia, 
emaciation,  fever,  and  cachexia)  are  developed — there  is,  of  course, 
no  difficulty ;  but  in  some  cases  of  the  disease,  the  generalised 
glandular  enlargement  is,  as  we  have  seen,  preceded  by  a  stage 
in  which  the  glandular  swelling  is  local.  Now  in  such  cases, 
so  long  as  the  glandular  enlargement  is  localised,  it  is  im- 
possible to  distinguish  the  condition  from  simple,  local,  non- 
malignant  lymphoma  by  any  means  with  which  we  are  at  present 
acquainted.  The  local  glandular  enlargement  may  present  exactly 
the  same  characters  in  both  conditions — it  may  be  painless,  non- 
suppurative, non-caseating,  the  individual  glandular  nodules  being 
isolated,  and  not  adherent  either  to  one  another  or  to  the  surround- 
ing parts. 

So  long  as  the  glandular  enlargement  presents  these  characters, 
and  is  localised  and  limited  to  one  group  of  glands,  we  may  hope 
that  it  is  merely  a  simple,  local,  non-malignant  lymphoma,  but  we 
cannot  positively  assert  that  it  may  not  be  the  precursor  of  a 
generalised  glandular  enlargement,  in  other  words,  of  Hodgkin's 
disease. 


hodgkin's  disease.  203 

In  connection  with  the  differential  diagnosis  in  such  cases, 
Osier  makes  the  following  statement :  "  A  single  bunch  in  the 
neck,  particularly  if  sub-maxillary,  persisting  for  over  a  year  or 
eighteen  months  without  involvement,  however  slight,  of  the  glands 
on  the  same  or  the  opposite  side,  or  in  the  axilla,  is  almost  certainly 
non-malignant  lymphoma."  * 

The  whole  question  turns  upon  the  definition  and  meaning 
which  ought  to  be  attached  to  the  term  Hodgkin's  disease.  In 
those  cases  in  which  a  local  glandular  enlargement  has  existed  for 
a  considerable  period  of  time  (many  months  or  years)  as  a  mere 
local  enlargement,  and  has  ultimately  been  followed  by  Hodgkin's 
disease  (i.e.,  by  generalisation  of  the  glandular  swellings  and  con- 
stitutional symptoms),  it  would,  perhaps,  be  more  correct  to  say 
that  the  Hodgkin's  disease  followed  a  simple,  local,  non-malignant 
lymphoma,  than  to  affirm  that  the  primary,  local,  glandular  enlarge- 
ment was  one  and  the  same  throughout  the  whole  course  of  the 
case  (i.e.,  was  from  the  first  identical  with  that  characteristic  of 
Hodgkin's  disease). 

In  those  cases  in  which  a  local  glandular  enlargement  is 
followed,  soon  after  its  development,  by  enlargement  of  other  groups 
of  glands  (by  generalisation  of  the  glandular  enlargement)  and  by 
constitutional  symptoms,  there  is,  of  course,  no  difficulty  in  suppos- 
ing that  the  primary  (and  apparently  localised)  glandular  enlarge- 
ment was  in  reality  part  and  parcel  of  (the  first  stage  of)  the 
Hodgkin's  disease. 

The  differential  diagnosis  of  Hodgkin's  disease  and  of 
scrofulous  enlargement  of  the  lymphatic  glands  must  be  chiefly 
based  upon: — the  character  of  the  glandular  swellings;  the  presence 
or  absence  of  tubercular  lesions,  such  as  phthisis,  in  other  parts  of 
the  body  ;  the  condition  of  the  spleen  ;  the  presence  or  absence  of 
lymphoid  deposits  in  other  tissues  and  organs  ;  the  nature  of  the 
constitutional  symptoms  ;  and  the  family  history  and  hereditary 
tendencies  of  the  patient. 

The  glandular  enlargement  of  Hodgkin's  disease  is  usually  a 
firm,  more  or  less  hard,  painless  enlargement,  which  slowly  and 
gradually,  but  (in  most  cases)  progressively,  increases  in  size,  and 
which  (in  typical  cases)  has  no  tendency  to  soften,  suppurate,  or 
caseate  ;  the  individual  glands  can,  in  the  earlier  stages  of  the 
disease,  at  all  events,  be  felt  as  smooth,  round,  or  oval,  movable 
lumps,  which  are  neither  adherent  to  one  another  nor  to  the 
adjacent  parts. 

*  Pepper's  System  of  Medicine,  vol.  iii.,  p.  929. 


204  DISEASES   OF   THE    BLOOD   GLANDS. 

But  these  characters  are  not  invariably  present,  for  in  some 
cases  the  glandular  enlargements  are  soft  and  almost  fluctuating. 

The  glandular  enlargement  due  to  scrofula  is  usually  painful 
and  tender  to  the  touch,  and  tends — and  this  is  one  of  its  essential 
characteristics — to  soften,  caseate,  and  suppurate,  and  after  reaching 
a  certain  size  to  diminish  in  size  rather  than  to  increase,  but 
exceptions  to  this  statement  are  by  no  means  uncommon.  In 
typical  cases,  the  individual  (scrofulous)  glands  cannot  be  distinctly 
defined,  even  at  a  comparatively  early  stage  of  their  development ; 
they  tend  to  become  adherent  to  one  another,  and  to  the  surround- 
ing parts,  and  to  form  a  soft,  ill-defined  mass.  But  here  again 
it  must  be  remembered  that  in  some  cases  in  which  the  glandular 
enlargement  during  life  presents  all  the  characters  of  Hodgkin's 
disease  (rather  than  of  scrofula),  post-mortem  examination  shows 
that  the  condition  is  tubercular. 

The  skin  overlying  the  enlarged  glands  in  Hodgkin's  disease  is 
usually  natural  in  appearance,  whereas  in  scrofulous  cases  it  is 
usually  injected,  reddened  or  purple  in  colour,  and  often  altered  in 
texture. 

In  scrofulous  cases,  cicatrices,  indicative  of  former  suppuration, 
are  often  present. 

The  fact  that  the  glandular  enlargement  is  of  very  large  size, 
more  especially  when  there  is  no  appearance  of  softening  or 
suppuration,  is  in  favour  of  Hodgkin's  disease  rather  than  of 
scrofula  ;  but  exceptions  to  this  statement  are  not  very  uncommon. 

Marked  emaciation,  anaemia,  and  cachexia,  when  there  is  no 
suppuration  and  no  internal  tubercular  lesion,  such  as  phthisis,  to 
account  for  their  presence,  are  suggestive  of  Hodgkin's  disease. 

Enlargement  of  the  spleen,  in  the  absence  of  chronic  phthisis 
and  waxy  (amyloid)  degeneration,  is  strongly  in  favour  of  the 
glandular  enlargement  being  due  to  Hodgkin's  disease. 

A  marked  hereditary  tendency  to  scrofula  ;  the  existence  of 
scrofulous  lesions,  such  as  phthisis,  in  other  parts  of  the  body  ;  the 
presence  of  the  tubercle  bacillus  in  the  sputum  or  in  the  discharge 
from  any  inflamed  or  suppurating  gland  or  sinus  ;  the  fact  that  the 
glandular  enlargement  is  localised  {i.e.,  limited  to  one  group  of 
glands  or  to  groups  of  glands  which  are  in  direct  anatomical  con- 
tinuity) ;  and  non-enlargement  of  the  spleen  are,  in  addition  to  the 
other  points  which  have  been  enumerated  above  (see  the  special 
characters  of  enlarged  scrofulous  glands),  in  favour  of  scrofula. 

The  differential  diagnosis  of  Hodgkin's  disease,  and  of  scrofulous 
enlargement  of  the  lymphatic  glands  is  especially  difficult  in  the 
following  circumstances  : — 


HODGKIN  S   DISEASE.  205 

1.  In  the  early  stages  of  those  cases  of  Hodgkins  disease  in  which 
the  sub-maxillary  and  cervical  glands  are  the  only  glands  which  are 
affected. 

In  such  cases  the  diagnosis  must  be  based  upon  the  characters 
of  the  glandular  swellings  which  have  been  described  above, 
though  it  must  be  admitted  that  these  characters  are  not  con- 
clusive. 

In  those  cases  in  which  it  is  impossible  to  give  a  positive 
opinion  when  the  patient  first  comes  under  observation,  the 
physician  must  either  be  content  to  watch  the  future  progress  of 
the  case,  and  to  wait  for  the  development  of  distinctive  symptoms 
(generalisation  of  the  glandular  swellings  and  the  appearance  of 
constitutional  symptoms),  or  (as  I  have  in  some  recent  cases  done) 
have  some  of  the  enlarged  glands  removed  by  the  surgeon,  and  the 
true  nature  of  the  glandular  affection  definitely  determined. 

Another  method  of  diagnosis  which  has  recently  suggested 
itself  to  me,  but  which  I  have  not  as  yet  put  into  actual  practice,  is 
the  tuberculin  test — the  injection  of  Koch's  tuberculin  into  the 
body  of  the  patient  with  the  object  of  determining  whether  a  reaction 
results  or  not. 

2.  In  those  exceptional  cases  of  Hodgkin's  disease  in  which  some 
of  the  enlarged  glands  soften,  suppurate,  or  caseate. 

Under  such  circumstances,  a  differential  diagnosis  can  only  be 
made  by  a  careful  and  judicial  consideration  of  the  whole  facts  of 
the  case.  I  should  strongly  doubt  the  case  being  merely  one  of 
Hodgkin's  disease  if  several  of  the  glandular  swellings  were  to 
suppurate  or  caseate.  There  seems  reason  to  suppose  that  scrofula 
and  Hodgkin's  disease  may  (actively)  co-exist  in  the  same  patient  ; 
this  fact  must  not  be  forgotten  in  the  diagnosis  of  doubtful  cases. 

3.  In  those  exceptio7tal  cases  of  tubercular  disease  in  which  the 
glandular  affection  is  zvidespread  (the  inguinal  as  well  as  the 
cervical  and  axillary  glands,  for  example,  being  affected),  in  which 
the  individual  glands  remain  isolated,  and  in  which  they  are  firm, 
hard,  painless,  in  which  there  is  no  softening  and  suppuration  and  no 
adhesion  to  the  overlying  skin. 

Tubercular  cases  of  this  description  are  rare  ;  but  when  they  do 
occur  they  cannot,  so  far  as  I  know,  be  distinguished  during  life 
from  cases  of  Hodgkin's  disease,  unless  it  be  by  observing  whether 
they  react  or  not  to  the  hypodermic  injection  of  tuberculin ;  for  the 
clinical  characters  of  the  glandular  enlargement  are  identical  in 
both  cases. 

In  cases  of  this  kind,  the  age  of  the  patient,  his  hereditary 
tendencies  as  regards  tubercle,  the  presence  or  absence  of  marked 


206  DISEASES   OE   THE    BLOOD   GLANDS. 

enlargement  of  the  spleen  and  of  lymphoid  deposits  in  the  tonsils, 
skin,  etc.,  and  the  presence  or  absence  of  fever  may,  however,  as  I 
have  previously  pointed  out,  throw  some  light  upon  the  nature  of 
the  case. 

The  differential  diagnosis  of  Hodgkin's  disease  and  of 
cancerous  enlargement  of  the  lymphatic  glands. — Here  there 
is  seldom  any  great  difficulty. 

The  lymphatic  enlargement  due  to  cancer  is  usually  harder 
(more  cartilaginous,  stony,  and  knobby)  than  that  due  to  Hodgkin's 
disease.  The  glandular  enlargement  due  to  cancer  is  seldom,  if 
ever,  so  generalised  and  widespread  as  that  in  typical  cases  of 
Hodgkin's  disease.  In  cancer,  the  lymphatic  enlargement  is 
secondary  rather  than  primary ;  the  symptoms  and  signs  of  a 
primary  cancerous  lesion  on  the  surface  of  the  body  (skin,  mamma, 
etc.)  or  in  some  of  the  internal  organs,  such  as  the  stomach,  are 
therefore  usually  present ;  and  the  enlarged  glands  are  usually  in 
direct  anatomical  (lymphatic)  relationship  to  the  primary  growth! 

Enlargement  of  the  spleen  is  in  favour  of  Hodgkin's  disease  and 
against  cancer. 

In  doubtful  cases  the  age  of  the  patient  may  be  of  importance  : 
cancer  is  much  more  likely  to  occur  in  old  people. 

The  differential  diagnosis  of  Hodgkin's  disease  and  of 
true  malignant  sarcoma  of  the  lymphatic  glands. — Here  the 
distinction  is  often,  I  believe,  impossible  ;  it  is  probable,  I  think, 
that  some  of  the  cases  of  lymphatic  enlargement  which  are 
described  as  Hodgkin's  disease  are  in  reality  malignant  sarcomata. 

The  facts  that  the  lymphatic  enlargement  is  limited  to  one  or 
more  groups  of  lymphatic  glands  which  are  in  direct  anatomical 
continuity ;  that  the  lymphatic  swellings  directly  invade  the 
surrounding  tissues  ;  that  such  organs  as  the  mamma  and  testicle 
are  affected  ;  and  especially  that  the  lymphatic  enlargements  are 
secondary  to  a  primary  tumour  in  these,  or  in  some  of  the  internal 
organs  ;  and  that  the  spleen  is  not  enlarged — are  in  favour  of 
true  malignant  sarcoma  of  the  lymphatic  glands  rather  than  of 
Hodgkin's  disease. 

Vice  versa,  widespread  enlargement  of  several  groups  of 
lymphatic  glands  in  different  parts  of  the  body  ;  the  absence  of  a 
primary  tumour  ;  enlargement  of  the  spleen  ;  the  early  develop- 
ment of  cachexia  ;  implication  of  the  tonsils  and  other  organs  in 
which  lymphoid  tissue  normally  abounds,  are  in  favour  of  Hodgkin's 
disease. 

The  differential  diagnosis  of  Hodgkin's  disease  and  of  true 
malignant  sarcoma  is  especially  difficult,  in  fact,  impossible  during 


hodgkin's  disease.  207 

life  in  many  of  the  cases  in  which  the  glandular  enlargement  is 
internal — i.e.,  in  which  the  bronchial  and  mediastinal  glands  are 
affected.  In  the  present  position  of  therapeutics  this  point  of 
differential  diagnosis  is  of  no  importance  to  the  practical  physician; 
in  such  cases  it  is  a  matter  of  indifference,  so  far  as  prognosis  and 
treatment  are  concerned,  whether  the  glandular  enlargement  is  due 
to  a  true  malignant  sarcoma  or  to  Hodgkin's  disease;  for  we  are 
unable  by  any  therapeutic  means,  with  which  we  are  at  present 
acquainted,  to  cure  either  the  one  affection  or  the  other. 

In  his  work  on  the  clinical  examination  of  the  blood,  Cabot 
makes  the  following  statements  with  regard  to  the  nature  of 
Hodgkin's  disease  and  its  diagnosis.  The  subject  is  one  of  so 
much  difficulty,  and,  in  the  present  position  of  our  knowledge,  of  so 
much  uncertainty,  that  I  quote  his  remarks  in  full  : — 

"  The  diagnosis  of  this  disease  is  impossible  without  the  blood  count.  Its 
pathology  is  identical  with  that  of  leukaemia,  and  even  post-mortem  the  two 
diseases  are  indistinguishable  so  far  as  the  lesions  outside  of  the  blood  are 
concerned.  Yet  the  blood  is  in  no  way  peculiar,  but  presents  in  most  cases  all 
the  characteristics  of  the  normal  tissue.  Its  value  is  as  negative  evidence, 
telling  us  in  a  given  case  that  leukaemia  is  absent  even  though  all  the  other 
signs  and  symptoms  may  be  those  of  leukaemia. 

(1.)  Transitions  from  Hodgkin's  disease  to  leukaemia  have  taken  place  under 
the  eyes  of  competent  observers,  but  they  are  very  rare.  Only  three  such  cases 
are  on  record  so  far  as  I  know,  that  of  Fleischer  and  Penzoldt,*  that  of  Mosler,t 
and  one  reported  by  Senator,  %  where  two  sisters  came  under  observation,  both 
suffering  from  Hodgkin's  disease.  One  died  of  it  ;  in  the  other  the  blood 
changed  to  that  of  leukaemia  before  death. 

Doubtless  many  of  the  other  cases  supposed  to  exemplify  a  similar  transition 
were  really  cases  in  which  a  leucocytosis  arose  owing  to  some  inflammatory 
complication,  as  not  uncommonly  occurs. 

From  the  existence  of  these  very  rare  cases  of  a  transition  to  leukaemia  it 
has  been  supposed,  especially  by  French  observers,  that  Hodgkin's  disease  is 
simply  an  early  stage  of  true  leukaemia,  and  that  this  would  always  become 
apparent  were  it  not  that  the  patients  die  of  some  intercurrent  disease  before 
the  signs  of  leukaemia  have  time  to  show  themselves  in  the  blood.  One  difficulty 
with  this  view  is,  that  there  occur  chronic  cases  which  last  from  eight  to  ten 
years  without  any  change  in  the  blood.  Another  difficulty  is,  that  the  transition 
is  in  fact  rare  despite  the  relative  frequency  with  which  the  disease  is  met  with. 

(2.)  Undoubtedly  many  cases  diagnosed  as  Hodgkin's  disease  are  in  fact 
cases  of  glandular  hypertrophy  due  to  syphilis  or  tuberculosis,  and  this  fact  has 
led  many  to  the  belief  that  all  cases  called  Hodgkin's  disease  are  in  reality  only 
syphilitic  or  tubercular  adenitis.  In  a  considerable  number  of  cases,  however, 
tuberculosis  has  been  disproven  by  careful  inoculation  experiments  with  the 
glandular  tissue,  and  there  is  no  reasonable  doubt  that  some  cases  at  any  rate 


*  Deut.  Arch.  f.  klin.  Med.,  vol.  17. 

t  Ziemssen's  "  Handbuch  d.  Path,  und  Therap.,"  vol.  8. 

%  Berl.  klin.  Woch.,  1882,  p.  533. 


208  DISEASES   OF   THE   BLOOD   GLANDS. 

are  not  due  to  tuberculosis  or  syphilis.  Probably  the  diagnosis  can  never  be 
made  with  absolute  certainty  during  life. 

(3.)  The  frequent  occurrence  of  fever  and  other  symptoms  characteristic 
of  an  infectious  disease  has  led  some  writers  to  class  it  as  such.  In  a  certain 
percentage  of  cases  the  disease  (like  leukaemia)  has  run  an  acute  course,  lasting 
not  more  than  six  weeks  from  the  first  symptom  to  death.  In  some  chronic 
cases  the  same  sort  of  evidence  of  an  infectious  nature  has  been  brought  forward. 
Ulcerations  occur  in  the  mouth  and  intestine  through  which  morbid  products 
might  gain  admission.  Various  bacteria  (pyogenic  and  others)  have  been  found 
in  the  blood  and  tissues  from  time  to  time,  but  numerous  negative  examinations 
for  micro-organisms  are  also  on  record,  and  the  evidence  is  insufficient  to 
establish  the  infectious  nature  of  the  disease.  None  the  less,  there  is  a  growing 
tendency,  among  the  leading  writers  and  observers  in  Germany  and  elsewhere, 
to  believe  that  the  disease  will  ultimately  be  shown  to  be  infectious. 

(4.)  Meantime  most  surgeons  continue  to  regard  it  as  a  form  of  sarcoma, 
and  to  treat  it  like  malignant  disease."  * 

The  differential  diagnosis  of  Hodgkin's  disease  and  of 
leucocythaemia  has  already  been  considered  (see  p.  167). 

Prognosis. 

In  undoubted  cases  of  Hodgkin's  disease  the  prognosis  is  most 
unfavourable  ;  so  far  as  is  at  present  known,  the  disease  almost 
invariably  terminates  sooner  or  later  in  death.  So  long  as  the 
glandular  enlargement  is  local,  the  prognosis  is,  of  course,  much 
more  favourable  ;  but,  as  I  have  previously  pointed  out,  it  is  often 
impossible  at  this  stage  of  the  disease  to  distinguish  the  condition 
from  simple,  local,  non-malignant  lymphoma. 

In  trying  to  form  a  correct  estimate  of  the  probable  duration  of 
the  disease  in  any  particular  case,  after  the  glandular  enlargement 
has  become  generalised,  the  following  points  have  to  be  taken  into  • 
account : — (1)  The  length  of  time  the  disease  has  already  existed  ; 
(2)  the  rapidity  with  which  it  appears  to  be  progressing ;  (3)  the 
position  of  the  glandular  groups  which  are  chiefly  affected  ;  (4)  the 
presence  or  absence  of  complications  ;  (5)  the  state  of  the  patient's 
health  prior  to  the  onset  of  the  disease  ;  (6)  the  age  of  the  patient ; 
and  (7)  the  effects  of  treatment. 

The  simultaneous  enlargement  of  many  different  glandular 
groups ;  the  rapid  enlargement  of  the  affected  glands ;  the  early 
development  of  constitutional  symptoms ;  the  fact  that  the  asthenia, 
anaemia,  emaciation,  fever,  and  cachexia  are  pronounced  ;  the  fact 
that  the  enlarged  glands  are  pressing  upon  and  interfering  with  the 
function  of  important  structures,  such  as  the  respiratory  passages, 
the  oesophagus,  etc.;  the  fact  that  the  bronchial  and  mediastinal 

*  "Clinical  Examination  of  the  Blood,"  p.  154. 


HODG KIN'S   DISEASE.  209 

glands  are  involved;  the  presence  of  grave  symptoms,  such  as  great 
dyspnoea,  general  dropsy,  ascites,  etc.,  and  of  serious  complications 
such  as  pleurisy,  pericarditis,  pneumonia,  diphtheria,  etc. ;  the  facts 
that  the  patient  is  old,  and  that  prior  to  the  onset  of  the  disease  he 
was  in  bad  health  ;  and  the  fact  that  there  is  no  improvement 
under  treatment,  are  highly  unfavourable  indications,  and  suggest 
that  the  duration  of  the  case  will  be  short. 


Treatment. 

In  the  present  state  of  our  therapeutic  knowledge  the  treatment 
of  Hodgkin's  disease  is  a  most  unsatisfactory  subject.  So  far  as  I 
know,  arsenic  is  the  only  remedy  which  is  of  any  use,  once  the 
glandular  enlargements  have  become  generalised.  I  am  satisfied 
that  in  two  cases  of  the  disease  which  were  under  my  own  observa- 
tion, temporary  arrest  in  the  development  of  the  glandular  swelling, 
and  marked,  though  temporary,  improvement  in  the  constitu- 
tional symptoms,  occurred  under  the  use  of  this  drug.  But  in 
both  cases  the  improvement  was  merely  temporary.  In  both  cases 
after  three  or  four  months,  the  disease  appeared  to  take  on  new 
activity ;  both  cases  terminated  fatally.  The  drug  may  be  given 
either  by  the  mouth,  or  it  may  be  injected  into  the  enlarged  glands. 
I  have  no  personal  experience  of  the  subcutaneous  method.  In  all 
cases  I  have  given  the  drug  by  the  mouth,  in  the  form  of  Fowler's 
solution,  well  diluted.  I  begin  with  a  small  dose  (two  or  three 
drops),  and  gradually  increase  the  dose  until  the  maximum  quantity 
which  can  be  satisfactorily  borne  is  reached.  The  object  is  to 
saturate  the  system  with  arsenic  without  producing  toxic  symp- 
toms. Should  toxic  symptoms  arise,  the  remedy  should  be 
discontinued  for  a  time,  and  then,  after  an  interval,  again  admini- 
stered in  small  doses.  It  might  be  expected  that  the  injection  of 
the  drug  into  the  enlarged  glands  would  produce  irritation  and  in- 
flammation, but  this  is  certainly  not  always  the  case  ;  indeed,  a  case 
which  I  have  figured  and  detailed  in  my  Atlas  of  Clinical  Medicine 
(Plate  VIII),  shows  that  very  large  doses  may,  in  some  cases,  be 
injected  into  the  enlarged  glands  without  producing  any  untoward 
effects.  In  that  case  Dr  Handford  injected  as  much  as  thirty 
drops  of  Fowler's  solution  into  the  enlarged  glands,  daily ;  the 
injections  did  not  cause  any  local  irritation  or  inflammation  ; 
though  after  a  time  they  did  produce  disturbance  of  the 
stomach. 

In  treating  cases  of  Hodgkin's  disease,  the  general  health  must,  of 
course,  be  kept  in  the  highest  possible  state  of  efficiency.    The  patient 

O 


210  DISEASES   OF   THE    BLOOD    GLANDS. 

should  be  carefully  and  well  fed,  well  clothed,  well  housed,  and 
diligently  protected  from  cold  and  all  causes  of  depression.  During 
the  summer  months  he  should  spend  as  much  of  his  time  as 
possible  in  the  open  air,  and  especially  at  the  seaside — for  in  some 
cases  sea  air  has  seemed  to  be  beneficial  (it  is  highly  probable  that 
some  of  these  cases  were  tubercular). 

Cod-liver  oil,  quinine,  and  Easton's  syrup  are,  in  addition  to 
arsenic,  perhaps  the  most  useful  remedies  which  we  possess.  I 
have  no  personal  experience  of  phosphorus,  but  its  administra- 
tion appears  to  have  been  followed  by  temporary  improvement  in 
some  cases.  Possibly  the  interstitial  injection  of  chloride  of  zinc, 
which  has  recently  been  introduced  by  M.  Lannelongue  for  the 
treatment  of  tuberculosis,  may  be  beneficial.  Iodide  of  potassium 
and  the  syrup  of  iron  have  not,  in  my  hands,  yielded  any  good 
result ;  and  this  appears  to  be  the  experience  of  almost  all 
observers. 

Local  counter-irritation  (by  iodine,  blisters,  the  iodide  of 
mercury  ointment,  etc.)  seems  to  be  of  little  or  no  use.  Cold 
douches  applied  to  the  enlarged  glands,  friction  and  massage  have 
been  recommended  by  some  authorities,  but  at  the  best  they  can 
be  merely  palliatives.  Galvano-puncture  has  been  employed,  but 
without  benefit  ;  the  application  of  the  constant  electric  current  to 
the  enlarged  glands,  with  the  object  of  producing  absorption  of 
the  lymphoid  tissue  and  promoting  a  healthier  state  of  nutrition  in 
the  diseased  glands,  is  of  very  doubtful  value. 

Excision  of  the  enlarged  glands  is  useless  once  the  glandular 
enlargement  has  become  generalised. 

In  those  cases  in  which  the  glandular  enlargement  is  local, 
excision  is  advisable,  provided  that  the  glandular  mass  can  be 
safely  and  satisfactorily  removed  by  operation. 

The  difficulty  of  distinguishing  the  glandular  enlargement  due 
to  simple  non-malignant  lymphoma  and  that  due  to  Hodgkin's 
disease,  in  its  early  localised  stage,  has  already  been  insisted  upon. 
Excision  of  a  simple  adenoma,  provided  that  the  tumour  can  be 
safely  and  satisfactorily  removed,  though  it  may  not  be  absolutely 
necessary,  can  do  no  harm  ;  should,  however,  the  glandular 
cnlargement  be  due  to  Hodgkin's  disease,  excision  is  eminently 
advisable  while  the  lymphatic  swelling  is  still  localised ;  the 
operation  may,  perhaps,  give  the  patient  a  chance  of  recovery. 
But  owing  to  the  difficulty  of  distinguishing  simple  lymphoma  and 
the  glandular  enlargement  of  Hodgkin's  disease,  conclusions  based 
upon  the  successful  removal  of  lymphatic  enlargements,  supposed 
to  be  due  to  Hodgkin's  disease,  are  apt  to  be  fallacious. 


HODGKINS   DISEASE.  211 

In  one  case,  in  which  a  glandular  enlargement  in  the  neck  and 
thorax  presented  all  the  clinical  characters  of  Hodgkin's  disease, 
the  glandular  enlargement  has  subsided  and  the  patient  gained 
strength  and  weight  under  the  administration  of  thyroid  extract, 
arsenic  and  cardiac  tonics  internally,  and  the  application  of  iodide 
of  potassium  ointment  externally. 


ADDISON'S    DISEASE. 

Definition  or  Short  Description. — Addison's  disease,  to  which 
the  synonyms  Morbus  Addisonii,  Melasma  supra-renale,  Bronzed- 
skin  disease,  Maladie  bronzee,  Asthenie  surrenale,  etc.,  have  been 
given,  is  a  distinct  clinical  entity,  characterised  during  life  by 
certain  well-marked  symptoms  (of  which  asthenia,  remarkable 
feebleness  of  the  heart's  action  and  of  the  pulse,  vomiting,  pains  in 
the  abdomen  and  back,  and  pigmentation  of  the  skin  and  mucous 
membranes,  are  the  chief),  and  associated  after  death  with  a  lesion 
of  the  suprarenal  capsules  (usually  a  fibro-caseous  destruction  of 
both  capsules). 

The  onset  of  the  disease  is  usually  slow  and  insidious,  and  the 
course  is  usually  chronic,  though  in  exceptional  cases  the  onset  is 
more  acute  and  the  course  rapid.  The  disease  is  almost  invariably 
fatal,  though  recovery  does  appear  to  have  occurred  in  very  rare 
instances. 

That  the  disease  is  a  distinct  clinical  entity  is  conclusively 
proved  by  the  fact  that  over  and  over  again,  in  instances  too 
numerous  to  mention,  the  existence  of  the  capsular  lesion  has 
been  predicted  (because  of  the  presence  of  the  symptoms  enume- 
rated above)  during  life,  and  the  presence  of  the  capsular  lesion 
has  been  demonstrated  after  death,  without  any  other  local  change 
or  visceral  lesion  capable  of  explaining  the  clinical  symptoms,  or 
sufficient  to  account  for  the  fatal  issue. 

There  is  still  much  difference  of  opinion  as  to  the  pathological 
physiology  of  the  disease,  i.e.,  as  to  the  exact  manner  in  which  the 
symptoms  are  produced,  the  relationship  of  the  symptoms  to  the 
lesion  of  the  capsules  and  to  the  lesions  in  the  sympathetic  nervous 
system  which  are  present  in  many  cases  of  the  disease. 

Historical  Note. — The  celebrated  physician,  Dr  Addison, 
directed  attention  to  the  relationship  of  anaemia  and  diseases  of 
the  suprarenal  capsules  in  the  year  1849,  though  he  did  not  pub- 
lish his  well-known  treatise,  entitled  On  the  Constitutional  and 
Local  Effects  of  Disease  of  the  Suprarenal  Capsules,  until  1855. 
His   description  of  the  symptoms  was  singularly  complete,    and 


ADDISON'S   DISEASE.  213 

(with  some  few  additions)  practically  represents  our  clinical  know- 
ledge at  the  present  time  (see  infra). 

Cases  of  Addison's  disease  had  undoubtedly  been  observed  and 
recorded  before  the  year  1849,  though  the  connection  between  the 
symptoms  and  the  lesion  of  the  capsules  does  not  seem  to  have 
been  suspected.  Thus  Dr  Frederick  P.  Henry,  in  the  historical 
summary  which  he  gives  of  the  disease,  states  : — "  The  first  case  of 
Addison's  disease  on  record  is  to  be  found  in  Lobstein's  treatise, 
De  nervi  sympathici  humani  fabrica  et  morbis,  Paris,  1823,  from  the 
English  translation  of  which,  by  the  late  Professor  Joseph  Pancoast, 
I  take  the  following  extract :  '  I  have  myself  observed  the  nerves 
forming  the  suprarenal  plexus  much  thickened  in  disease,  where 
the  suprarenals,  which  were  more  than  twice  as  large  as  usual,  had 
degenerated  into  tuberculous  substance.  The  patient  was  an  un- 
married woman,  twenty-five  years  of  age,  who  died  in  convulsive 
spasms  analogous  to  the  epileptic.  .  .  .  Nothing  unusual  was 
discovered  in  the  body  of  this  woman,  but  the  aforesaid  change  in 
the  suprarenal  glands  and  the  enlargement  of  the  nerves.'  Not- 
withstanding," says  Dr  Henry,  "  the  fact  that  there  is  no  record  of 
the  darkening  of  the  complexion,  the  above  was  undoubtedly  a 
typical  case  of  Addison's  disease,  in  which,  moreover,  death  by 
convulsions  is  not  uncommon.  The  observation  regarding  the 
thickening  of  the  nerves  in  this,  the  first  recorded  instance  of  the 
disease,  is  of  remarkable  interest.  The  second  case  was  recorded 
in  the  Halle  Hospital  Reports,  by  Dr  Schotte,  in  October  1823, 
and  is  published  in  vol.  vii.  of  the  Deutsches  Archiv.f.  klin.  Med.,  by 
Risel,  in  the  course  of  his  article  Zur  Patholo°ie  des  Morbus  Addi- 
sonii.  The  third  case  came  under  the  observation  of  Dr  Richard 
Bright,  at  Guy's  Hospital,  in  1829.  It  is  contained  in  Bright's 
classical  Reports  of  Medical  Cases,  and  also  figures  as  Case  v.  in 
Addison's  original  memoir.  The  lesions  of  the  capsules  were 
characteristic  ;  there  was  no  other  affection  of  any  consequence, 
and  for  the  first  time  in  the  history  of  the  disease,  it  was  noted 
that  the  complexion  was  very  dark.  A  few  other  cases  were 
reported  before  the  year  1855,  when  Addison  published  his  work 
On  the  Constitutional  and  Local  Effects  of  Disease  of  the  Supra- 
renal Capsules,  but  it  was  reserved  for  his  sagacity  to  detect  the 
relation  between  the  well-marked  constitutional  symptoms  of  the 
affection,  the  peculiar  pigmentation  of  the  skin,  and  the  structural 
changes  in  the  suprarenal  capsules."* 

From  these  statements  it  will  be  apparent  that  Addison  was  the 
first  to  give  a  detailed  description  of  the  clinical  symptoms  of  the 
disease,  and  to  show  that  the  lesion  in  the  suprarenal  capsules  and 
the  well-marked  and  characteristic  clinical  symptoms  are  associated 
as  cause  and  effect. 


Buck's  Reference  Handbook  of  the  Medical  Sciences,  vol.  i.,  p.  74. 


2  14  DISEASES   OF   THE   BLOOD    GLANDS. 

Further,  it  must  be  noted  that  Addison's  discovery  of  the  rela- 
tionship of  the  symptoms  of  the  disease  to  the  lesion  of  the 
capsules  was  not  merely  a  happy  hit — it  was  no  mere  fluke — but 
was  the  outcome  of  a  well-planned  and  deliberate  search,  the  object 
of  which  was  to  discover  the  cause  of  that  form  of  anaemia  which 
he  termed  idiopathic — the  pernicious  ancemia  of  the  present  time. 

Etiology. 

In  the  great  majority  of  cases  of  Addison's  disease  the  lesion 
of  the  capsules  is  tubercular.  Hence  it  may  be  assumed  that  con- 
ditions which  favour  the  production  of  tubercle  in  other  parts  of 
the  body  predispose  to  the  production  of  Addison's  disease. 

Age. — The  disease  is  most  frequently  met  with  between  the 
ages  of  twenty  and  forty  ;  it  is  exceedingly  rare  before  ten,  and  after 
fifty  years  of  age.  Cases  are,  however,  occasionally  met  with  in 
children  and  in  old  people.  In  a  case  which  I  have  at  present 
under  observation  the  patient  is  aged  eight  and  a  half  years  (see 
Case  VI.).  Dr  T.  W.  M'Dowall,  of  the  Northumberland  County 
Asylum,  sent  me  a  few  years  ago  the  suprarenal  capsules  from  a 
case  which  terminated  fatally  at  the  age  of  seventy  ;  in  that  case,  in 
which  the  lesion  was  quite  typical,  it  seems  certain  that  the  disease 
must  have  developed  after  the  age  of  sixty-one. 

Sex. — Males  are  much  more  frequently  affected  than  females. 
Of  183  unequivocal  cases  collected  by  Greenhow,  119  (or  65  per 
cent.)  were  males,  and  64  (or  35  per  cent.)  females  ;  of  127  cases 
analysed  by  Jaccoud,  79  (or  62  per  cent.)  were  males,  and  48  (or  38 
per  cent.)  females.     In  my  12  cases,  7  were  males  and  5  females. 

Occupation  :  Social  Position. — The  great  majority  of  cases  of 
the  disease  occur  in  hospital  patients,  amongst  the  working  classes 
and  lower  orders  of  society,  and  especially  in  those  whose  occupation 
exposes  them  to  injury  and  strain. 

Blows  and  injuries  to  the  back  seem  undoubtedly  to  be  the 
exciting  cause  of  the  disease  in  a  certain  proportion  of  cases  ;  and 
this  is  just  what  one  might  expect  seeing  that  the  lesion  is  tuber- 
cular. There  can  be  no  doubt  that  local  injury  (probably  by 
affording  a  suitable  nidus  for  the  development  of  the  tubercle 
bacillus  or  its  spores,  which  are  already  in  the  body)  may  favour 
the  production  of  tubercular  lesions  in  some  organs — such,  for 
example,  as  tubercular  tumours  in  the  cerebellum.  In  my  12  cases, 
a  definite  history  of  injury  to  the  back  could  only  be  obtained  in 
one  case. 

So  much  difference  of  opinion  still  exists  regarding  the  patho- 


ADDISON'S   DISEASE.  21 5 

logical  physiology  of  Addison's  disease,  that  it  will  perhaps  be 
advisable,  before  describing  the  morbid  anatomy  and  pathology,  to 
consider  the  clinical  history  of  the  disease. 

Clinical  History. 

Although  a  large  number  of  cases  of  morbus  Addisonii  have 
been  recorded  during  the  past  forty-three  years,  and  many  im- 
portant papers  and  monographs  have  been  written  on  the  subject, 
the  original  description  of  the  disease  which  Addison  published  in 
the  year  1855  remains  singularly  complete,  and  (with  some  addi- 
tions) practically  represents  our  clinical  knowledge  at  the  present 
time.  The  following  is  his  description  of  the  disease  (I  omit  the 
paragraphs  relating  to  idiopathic  anaemia  which  have  already  been 
quoted  on  page  57)  : — 

Addison's  description  of  the  disease. — "  It  was  whilst  seeking 
in  vain  to  throw  some  additional  light  upon  this  form  of  anaemia 
that  I  stumbled  upon  the  curious  facts  which  it  is  my  more  im- 
mediate object  to  make  known  to  the  profession  ;  and  however 
unimportant  or  unsatisfactory  they  may  at  first  sight  appear,  I 
cannot  but  indulge  the  hope  that,  by  attracting  the  attention  and 
enlisting  the  co-operation  of  the  profession  at  large,  they  may  lead 
to  the  subject  being  properly  examined  and  sifted,  and  the  inquiry 
so  extended  as  to  suggest,  at  least,  some  interesting  physiological 
speculation,  if  not  still  more  important  practical  indications. 

"  The  leading  and  characteristic  features  of  the  morbid  state  to 
which  I  would  direct  attention  are — anaemia,  general  languor  and 
debility,  remarkable  feebleness  of  the  heart's  action,  irritability  of 
the  stomach,  and  a  peculiar  change  of  colour  in  the  skin,  occurring 
in  connection  with  a  diseased  condition  of  the  '  supra-renal 
capsules.' 

"  As  has  been  observed  in  other  forms  of  anaemic  disease,  this 
singular  disorder  usually  commences  in  such  a  manner  that  the 
individual  has  considerable  difficulty  in  assigning  the  number  of 
weeks,  or  even  months  that  have  elapsed  since  he  first  experienced 
indications  of  failing  health  and  strength  ;  the  rapidity,  however, 
with  which  the  morbid  change  takes  place  varies  in  different 
instances. 

"  In  some  cases  that  rapidity  is  very  great,  a  few  weeks  proving 
sufficient  to  break  up  the  powers  of  the  constitution,  or  even  to 
destroy  life,  the  result,  I  believe,  being  determined  by  the  extent, 
and  by  the  more  or  less  speedy  development,  of  the  organic  lesion. 

"  The  patient,  in  most  of  the  cases  I  have  seen,  has  been 
observed  gradually  to  fall  off  in  general  health  ;  he  becomes  languid 
and  weak,  indisposed  to  either  bodily  or  mental  exertion  ;  the  appe- 
tite is  impaired  or  entirely  lost  ;  the   whites   of  the   eyes  become 


2l6  DISEASES   OF   THE   BLOOD   GLANDS. 

pearly  ;  the  pulse  small  and  feeble,  or  perhaps  somewhat  large,  but 
excessively  soft  and  compressible  ;  the  body  wastes,  without 
however  presenting  the  dry  and  shrivelled  skin  and  extreme 
emaciation  usually  attendant  on  protracted  malignant  disease  ; 
slight  pain  or  uneasiness  is  from  time  to  time  referred  to  the  region 
of  the  stomach,  and  there  is  occasionally  actual  vomiting,  which  in 
one  instance  was  both  urgent  and  distressing  ;  and  it  is  by  no 
means  uncommon  for  the  patient  to  manifest  indications  of  dis- 
turbed cerebral  circulation. 

"  Notwithstanding  these  unequivocal  signs  of  feeble  circulation, 
anaemia,  and  general  prostration,  neither  the  most  diligent  inquiry 
nor  the  most  careful  physical  examination  tend  to  throw  the 
slightest  gleam  of  light  upon  the  precise  nature  of  the  patient's 
malady  ;  nor  do  we  succeed  in  fixing  upon  any  special  lesion  as 
the  cause  of  this  gradual  and  extraordinary  constitutional  change. 

"  We  may,  indeed,  suspect  some  malignant  or  strumous  disease 
— we  may  be  led  to  inquire  into  the  condition  of  the  so-called 
blood-making  organs — but  we  discover  no  proof  of  organic  change 
anywhere — no  enlargement  of  spleen,  thyroid,  thymus,  or  lymphatic 
glands — no  evidence  of  renal  disease,  of  purpura,  of  previous 
exhausting  diarrhcea,  or  ague,  or  any  long-continued  exposure  to 
miasmatic  influences  ;  but  with  a  greater  or  less  manifestation  of 
the  symptoms  already  enumerated,  we  discover  a  most  remarkable 
and,  so  far  as  I  know,  characteristic  discoloration  taking  place  in 
the  skin — sufficiently  marked,  indeed,  as  generally  to  have  attracted 
the  attention  of  the  patient  himself  or  of  the  patient's  friends. 

"  This  discoloration  pervades  the  whole  surface  of  the  body,  but 
is  commonly  most  strongly  manifested  on  the  face,  neck,  superior 
extremities,  penis,  and  scrotum,  and  in  the  flexures  of  the  axillae 
and  around  the  navel. 

"  It  may  be  said  to  present  a  dingy  or  smoky  appearance,  or 
various  tints  or  shades  of  deep  amber  or  chestnut-brown  ;  and  in 
one  instance  the  skin  was  so  universally  and  so  deeply  darkened, 
that  but  for  the  features  the  patient  might  have  been  mistaken  for 
a  mulatto. 

"  This  singular  discoloration  usually  increases  with  the  advance 
of  the  disease  ;  the  anaemia,  languor,  failure  of  appetite,  and  feeble- 
ness of  the  heart,  become  aggravated  ;  a  darkish  streak  usually 
appears  on  the  commissure  of  the  lips  ;  the  body  wastes,  but  with- 
out the  emaciation  and  dry,  harsh  condition  of  the  surface,  so 
commonly  observed  in  ordinary  malignant  diseases  ;  the  pulse 
becomes  smaller  and  weaker  ;  and,  without  any  special  complaint 
of  pain  or  uneasiness,  the  patient  at  length  gradually  sinks  and 
expires." 

Detailed  description  of  the  symptoms  of  Addison's  disease. 

— The  symptoms  of  Addison's  disease,  or,  to  speak  more  accurately, 
the  chief  symptoms  and  signs  of  typical  and  uncomplicated  cases 
of  Addison's  disease,  may  be  described  as  partly  positive  and  partly 


ADDISON'S   DISEASE.  2\J 

negative  ;  and  may  for  the  purposes  of  description  be  arranged  in 
the  following  groups,  which  are  by  no  means  artificial  : — 

1.  Asthenia,  feebleness  of  the  action  of  the  heart,  and  the 
symptoms  and  signs  which  result  therefrom. 

2.  Nausea,  vomiting,  and  other  symptoms  indicative  of  gastro- 
intestinal irritation. 

3.  Pain,  and  in  some  cases  tenderness  on  pressure,  in  the 
epigastric,  hypochondriac,  and  lumbar  regions ;  in  other  words, 
symptoms  due  to  irritation  of  sensory  nerve  fibres  in  the  neigh- 
bourhood of  the  suprarenal  bodies. 

4.  Pigmentation  of  the  skin  and  mucous  membranes. 

5.  Anaemia. 

6.  Symptoms  due  to  derangement  of  the  cerebro-spinal  (more 
especially  the  cerebral)  nerve  apparatus,  such  as  headache,  anaes- 
thesia, muscular  tvvitchings,  delirium,  convulsions,  etc. 

7.  The  absence  of  any  elevation  of  temperature  ;  in  fact,  in  most 
cases  the  presence  of  a  subnormal  temperature. 

8.  The  absence  of  any  marked  emaciation. 

9.  The  absence  of  symptoms  and  signs  indicative  of  local 
organic  disease  (other  than  the  disease  of  the  suprarenal  capsules) 
to  account  for  the  asthenia  and  other  symptoms  which  characterise 
the  condition. 

It  must  of  course  be  distinctly  understood  that  all  of  these 
symptoms  are  not  necessarily  present  even  in  typical  and  uncom- 
plicated cases  of  the  disease.  Thus,  the  anaemia  is  in  some  cases 
only  slight,  in  others  absent ;  in  some  cases  there  is  marked  wast- 
ing (loss  of  weight  and  muscle)  ;  in  others,  pain  in  the  back  is 
absent,  etc. 

Let  us  now  consider  some  of  the  more  important  symptoms 
individually  and  in  detail. 

Asthenia  and  Feebleness  of  the  Action  of  the  Heart. — 
Asthenia  is  the  most  constant,  and  consequently,  in  some  respects, 
the  most  important  symptom  of  Addison's  disease.  Although  it 
varies  considerably  in  degree  in  different  cases,  and  indeed  often 
very  notably  from  time  to  time  in  the  same  case,  it  is  the  one 
symptom  which  is  never  altogether  absent  in  well-marked  cases  of 
the  disease  ;  usually,  too,  it  is  the  first  symptom  of  which  the 
patient  makes  complaint.  Now,  since  in  most  cases  the  weakness 
is  developed  very  gradually,  since  it  usually  arises  insidiously, 
without  being  preceded  by  any  illness  or  other  obvious  exciting 
cause,  and  since  in  most  cases,  in  the  earlier  stages  of  the  disease  at 
all  events,  it  is  unattended  with  any  marked  loss  of  flesh,  it  seems 
reasonable  to  conclude  that  it  (the  asthenia),  and  the  lesion  of  the 


2l8  DISEASES   OE    THE    BLOOD    GLANDS. 

capsules  on  which  it  directly  or  indirectly  depends,  have  in  all 
probability,  in  many  cases  at  least,  been  gradually  and  slowly 
developing  for  months,  possibly  in  some  cases  for  years,  unknown 
to  the  patient.  This  statement  is  quite  in  accord  with  what  we 
know  of  the  morbid  anatomy  of  the  disease.  Many  cases  of 
Addison's  disease  have  been  reported,  in  which,  although  the  symp- 
toms were  only  of  a  few  months'  duration,  the  capsules  were  found 
after  death  to  be  completely  destroyed  and  in  an  advanced  stage  of 
casco-calcareous  degeneration.  In  such  cases,  as  Sir  Samuel  Wilks 
pointed  out  in  some  of  his  earlier  writings  on  the  subject,  the 
capsules  had,  in  all  probability,  been  destroyed  for  years  before  the 
date  at  which  the  disease  is  said  (from  the  clinical  history)  to  have 
commenced.  The  date  at  which  the  patient  first  complains  of 
symptoms,  and  the  date  at  which  a  disease  commences  and  at  which 
the  symptoms  actually  begin  to  develop  are,  as  I  have  pointed  out  in 
speaking  of  the  development  of  myxcedema,  not  always  synony- 
mous. Now  there  are  probably  no  cases  to  which  this  statement 
applies  with  greater  force  than  to  most  cases  of  Addison's  disease. 
The  onset  is  so  insidious,  and  the  loss  of  strength,  which,  be  it 
observed,  is  in  many  cases  the  only  symptom  at  the  commence- 
ment of  the  disease,  is,  in  the  earlier  stages  of  the  case,  so  slight, 
that  the  patient  slowly  and  insensibly,  as  it  were,  passes  from  a 
state  of  health  into  a  condition  of  disease.  It  is  probable,  I  think, 
that  in  many  cases  it  is  only  after  the  disease  has  been  in  existence 
for  some  considerable  time  that  the  languor  and  debility  become 
sufficiently  accentuated  to  attract  the  attention  of  the  patient,  or,  at 
all  events,  to  make  him  suspect  that  he  is  really  ill,  and  to  lead  him 
to  take  medical  advice. 

The  asthenia  seems  to  be  the  direct  result  of  the  lesion  of  the 
suprarenal  capsules. 

As  the  case  goes  on  the  asthenia  becomes  more  and  more 
marked,  and  the  patient  complains  of  feeling  "  weak,"  "  tired," 
"  languid,"  "  unfit  for  any  exertion,  either  of  body  or  mind,"  "  good 
for  nothing,"  "  quite  done  up,"  "  completely  exhausted,"  "  utterly 
prostrated,"  etc. 

Loss  of  vasomotor  nerve  tone  and  feebleness  of  the  heart's 
action  arc  important  features — I  am  disposed  to  think  perhaps  the 
most  important  features — of  the  disease. 

The  nerve  tone,  reserve  force,  recuperative  and  resisting  powers, 
soon  become  seriously  impaired  ;  and  comparatively  trivial  causes, 
such  as  slight  bodily  exertion,  mental  excitement,  an  ordinary  dose 
n{  purgative  medicine,  an  attack  of  vomiting,  or  a  trivial  intercur- 
rent illness,  which  in  a  healthy  man  would  cause  little  or  no  dis- 


ADDISON'S   DISEASE.  2IO, 

turbance,  may  produce  the  most  profound  prostration  and  exhaus- 
tion. This  lack  of  resisting  power  and  want  of  proper  recuperative 
energy  are,  from  a  therapeutic  point  of  view,  most  important  fea- 
tures of  the  disease.  In  more  than  one  of  the  recorded  cases  death 
resulted  from  an  ordinary  dose  of  purgative  medicine.  It  cannot  be 
too  forcibly  pointed  out,  that  in  the  treatment  and  management  of 
cases  of  Addison's  disease  it  is  of  paramount  importance  to  protect 
the  patient  from  everything  which  (in  him)  will  be  likely  to  cause 
exhaustion  and  depression.  There  can,  I  think,  be  little  doubt 
that  the  duration  of  many  cases  of  Addison's  disease  depends  upon 
the  nature  of  the  patients'  surroundings  and  the  care  with  which  the 
patients  are  protected  from  everything  likely  to  be  in  the  least 
injurious  and  to  produce  depression. 

Paroxysmal  exacerbations  of  the  debility  and  languor  are  of 
frequent  occurrence.  These  exacerbations  are  apparently  in  some 
cases  the  result  of  attacks  of  nausea  and  vomiting,  or  of  gastro- 
intestinal irritation,  to  which  I  will  presently  refer  in  more  detail. 

The  asthenia  is  reflected  externally  in  the  appearance  of  the 
patient ;  his  facial  expression  and  whole  bearing  are,  when  the 
disease  is  at  all  advanced,  suggestive  of  languor  and  debility. 

The  condition  of  the  heart  and  pulse  afford  corroborative  evi- 
dence of  this  depression. 

The  pulse  is  always  weak,  and  in  the  great  majority  of  cases 
small,  though  in  some,  as  Addison  himself  pointed  out,  it  is  full 
and  soft.  In  some  cases,  more  especially  in  the  later  stages,  the 
pulse  may  be  jerking  in  character.  The  same  condition  of  pulse  is 
seen  in  the  later  stages  of  some  cases  of  pernicious  ansemia. 

During  the  paroxysmal  attacks  of  exhaustion  and  depression, 
the  pulse  may  be  so  small  as  to  be  almost  or  even  entirely  imper- 
ceptible. The  feebleness  and  smallness  of  the  pulse  are  sometimes 
so  marked  that  the  condition  of  the  pulse  has  been  compared  to 
that  of  the  collapse  stage  of  Asiatic  cholera.  It  must,  however,  be 
noticed  that  in  many  cases  of  Addison's  disease  in  which  the  pulse 
is  imperceptible,  the  patient,  while  at  rest  and  in  the  recumbent 
position,  is  not,  strictly  speaking,  in  other  respects  collapsed.  But 
so  far  as  the  condition  of  the  heart  and  pulse  are  concerned,  many 
patients  in  the  advanced  stage  of  Addison's  disease  may  be  said  to 
be  in  a  constant  (chronic)  condition  of  collapse. 

The  weakness  of  the  action  of  the  heart  is  very  apparent  on 
physical  examination.  The  impulse  of  the  apex  beat  is  always 
feeble,  often  altogether  imperceptible  ;  the  heart  sounds  are  in 
many  cases  faint  and  distant.  In  some  cases,  the  area  of  cardiac 
dulness  appears  to  be  diminished  ;  after  death   the   heart  is  often 


220  DISEASES   OF   THE   BLOOD   GLANDS. 

found  to  be  smaller  than  normal.  This  atrophy  of  the  heart, 
which  has  been  recorded  in  several  cases,  and  which  was  present  in 
a  very  notable  degree  in  a  case  which  came  under  my  observa- 
tion a  few  years  ago,  has  hardly,  I  think,  received  the  attention 
which  it  deserves.  I  am  disposed  to  regard  it  as  a  very  important 
pathological  feature  of  the  disease. 

This  opinion  is  corroborated  by  the  experimental  observations  of 
Schafer  and  Oliver  ;  they  have  shown  that  the  medullary  portion 
of  the  suprarenal  capsules  contains  (secretes)  a  substance  which  has 
a  remarkably  stimulating  effect  upon  the  muscular  system,  and 
especially  upon  the  heart  and  arteries.  Consequently,  when  the 
secretion  of  the  suprarenal  capsules  is  suppressed,  we  would  expect 
muscular  weakness  and  atrophy,  and  especially  cardiac  muscular 
weakness,  to  be  developed. 

The  smallness  and  weakness  of  the  pulse  are  perhaps  not 
entirely  due  to  weak  action  of  the  heart.  In  many  cases  of  Addi- 
son's disease  there  is  disease  or  irritation  of  the  abdominal  sympa- 
thetic (the  suprarenal  and  solar  plexuses  of  nerves) ;  and  we  know 
that  irritation  of  the  abdominal  sympathetic  produces,  amongst 
other  results,  dilatation  of  the  blood-vessels  in  the  abdomen,  and 
that  this  overloading  of  the  abdominal  vessels  is  sometimes  so 
great  that  the  vessels  in  other  parts  of  the  body  are  depleted  of 
their  blood,  and  consequently  under-filled.  Possibly  the  smallness 
of  the  pulse  in  Addison's  disease  is  produced,  in  part  at  least,  in 
this  way. 

The  remarkable  feebleness  of  the  heart's  action,  and  the  inade- 
quate supply  of  blood  to  the  brain  and  peripheral  organs,  afford  a 
satisfactory  explanation  of  many  of  the  symptoms  which  are  met 
with  in  Addison's  disease.  The  palpitation  of 'the  heart  and  short- 
ness of  breath,  which  are  so  apt  to  occur  on  exertion,  the  tendency  to 
fainting,  the  giddiness  which  results  from  stooping  the  head  or 
suddenly  rising  from  the  recumbent  to  the  erect  position,  the 
temporary  disturbances  of  vision,  and  many  of  the  cerebral  symptoms, 
which  are  apt  to  occur  in  the  later  stages  of  the  disease,  are  doubt- 
less due  to  these  conditions. 

The  facility  with  which  cerebral  anaemia  and  fainting  are  pro- 
duced by  effort,  as,  for  example,  by  suddenly  rising  from  the 
recumbent  to  the  sitting  or  erect  position,  should  always  be  kept  in 
view.  Several  cases  have  been  reported  in  which  slight  efforts  have 
been  followed  by  fatal  syncope. 

Nausea,  Vomiting,  and  other  symptoms  indicative  of  Gastro- 
intestinal Irritation. —  In  almost  all  cases  of  Addison's  disease  the 
appetite  is   markedly  impaired,  and   in    some  entirely  lost.     Kuss- 


ADDISON'S   DISEASE.  221 

maul,  however,  has  recorded  a  case  in  which  there  was  an  insatiable 
appetite,  but  this  is  altogether  exceptional.  Some  patients  seem 
to  have  a  special  distaste  or  actual  repugnance  for  butcher's  meat. 
A  "sinking  feeling"  in  the  pit  of  the  stomach  is  often  complained 
of.     Thirst  is  in  some  cases  complained  of. 

Irritability  of  the  stomach,  sickness,  nausea,  retching,  and  vomiting 
are  highly  characteristic  symptoms,  and  are  present  in  most  cases 
of  the  disease  at  some  period  or  other  of  their  course.  The  nausea 
and  vomiting  are  usually  developed  after  the  asthenia,  but  in  some 
cases  they  are  the  first  symptoms  to  attract  the  attention  of  the 
patient. 

In  many  cases,  the  sickness  and  vomiting  occur  in  paroxysms, 
often  without  any  apparent  exciting  cause ;  the  vomiting  may  or 
may  not  be  associated  with  pain  or  tenderness  on  pressure  in  the 
epigastric  or  hypochondriac  regions.  In  more  than  one  case,  these 
attacks  have  appeared  to  me  to  resemble  most  closely  the  gastric 
crises  of  locomotor  ataxia.  The  attacks  of  sickness  and  vomiting 
are  often  accompanied  or  followed  by  intense  prostration  and 
depression.  The  vomited  matters  in  some  cases  contain  large 
quantities  of  mucus,  and  occasionally  (though  quite  exceptionally) 
blood.  It  may  be  pointed  out  in  this  connection  that  after  death 
the  stomach  has  often  been  found  to  contain  an  abnormal  amount 
of  mucus,  and  that  its  mucous  membrane  in  many  cases  shows 
distinct  evidence  of  irritation — it  may  be  deeply  congested, 
ecchymosed,  or  even  superficially  ulcerated. 

The  tongue  is  generally  clean  and  moist ;  it  is  often  pigmented 
in  the  manner  which  is  described  below. 

The  boivels  are  usually  constipated,  but  in  many  cases  diarrhoea 
is  very  readily  produced,  and  paroxysmal  attacks  of  diarrhoea 
occasionally  occur  without  any  apparent  cause.  This  tendency  to 
diarrhoea  should  always  be  borne  in  mind  ;  strong  purgatives 
should  never  be  given  in  Addison's  disease  ;  and  even  mild  aperients 
should  only  be  prescribed  with  the  greatest  care,  for  violent  diarrhoea, 
followed  by  intense  prostration,  and  even  death  itself,  have  been 
known  to  follow  an  ordinary  dose  of  purgative  medicine. 

The  spleen  has  in  many  cases  been  enlarged  after  death,  and  the 
increase  can,  in  some  cases,  be  detected  during  life. 

The  condition  of  the  liver  calls  for  no  special  remark. 

Pains  in  the  abdomen  and  back. — In  many  cases,  although 
the  fact  does  not  seem  to  have  come  under  Addison's  own  observa- 
tion, pain  and  sometimes  tenderness  on  pressure  are  experienced  in 
the  epigastric,  hypogastric,  or  lumbar  regions,  and  over  the  lower 
dorsal  or  lumbar  portions  of  the  spinal  column. 


2 22  DISEASES   OF   THE    BLOOD   GLANDS. 

These  pains' are  doubtless  due  to  irritation  of  the  suprarenal 
nerves  and  solar  plexus.  In  some  cases,  the  attacks  of  pain 
are  paroxysmal,  and  not  unfrequently  associated  with  nausea  and 
vomiting.  As  I  have  already  stated,  these  paroxysmal  attacks  of 
pain,  when  accompanied  by  nausea  and  vomiting,  may  resemble 
very  closely  the  gastric  crises  of  locomotor  ataxia. 

In  some  cases,  pain  is  complained  of  when  pressure  is  made 
from  behind  over  the  position  of  the  suprarenal  capsule. 

Dr  Greenhow  states  that  the  abdominal  pain  and  tenderness  are 
not  infrequently  associated  with  an  almost  spasmodic  rigidity  of  the 
abdominal  muscles,  as  if  they  were  instinctively  contracted  in  order 
to  protect  the  more  deeply-seated  parts  from  pressure. 

Pigmentation  of  the  skin  and  mucous  membranes. — Dis- 
coloration of  the  skin  and  mucous  membranes  (more  especially  of 
the  mucous  membrane  of  the  mouth)  is  perhaps  the  most  remark- 
able, and,  from  the  point  of  view  of  a  positive  diagnosis,  certainly 
the  most  important  symptom,  or  rather  sign,  of  Addison's  disease. 

It  must  however  be  remembered  that  the  pigmentation  is  by 
no  means  always  well  marked,  and,  in  fact,  in  some  rare  cases, 
especially  cases  which  run  an  unusually  rapid  course,  it  is  absent 
altogether. 

In  the  great  majority  of  cases,  the  pigmentation  is  developed 
either  subsequently  to,  or  simultaneously  with,  the  asthenia  and 
other  constitutional  symptoms  ;  as  a  general  rule,  the  pigmentation 
of  the  skin  is  not  noticed  until  the  asthenia  has  been  in  existence 
for  some  considerable  time  ;  but  numerous  cases  have  been  reported 
in  which  the  discoloration  of  the  skin  was  the  first  symptom  to 
attract  attention.  Thus,  in  a  case  reported  by  Dr  Rankin,*  dis- 
coloration of  the  face  and  hands  was  the  symptom  which  first 
attracted  the  attention  of  the  patient,  "  and  she  was  often  annoyed, 
when  making  calls,  by  friends  offering  her  water  to  wash  her 
hands."  Dr  Greenhow  gives  a  number  of  instances  in  which  the 
discoloration  of  the  skin  was  developed  several  months,f  and  in  one 
case,  it  is  said  even  as  much  as  eight  years,  before  the  asthenia  and 
other  characteristic  constitutional  symptoms  were  noticed.  But  it 
may  perhaps  be  doubted  whether  the  discoloration  of  the  forehead, 
face,  and  neck,  which  developed  in  this  remarkable  case  eight  years 
before  the  constitutional  symptoms  became  marked,  was  actually 
due  to  the  capsular  lesion. 

In   many  of  the  cases   in  which  the  pigmentation  is  the  first 


•  "  Medical  Times,"  24th  May  1856,  p.  518. 
t  "  Croonian  Lectures  on  Addison's  Disease,"  p.  20. 


ADDISON'S   DISEASE.  223 

symptom  to  attract  notice,  it  will,  I  suspect,  be  found  on  careful 
inquiry  that  a  certain  degree  of  asthenia  is  at  the  same  time  present ; 
the  very  gradual  and  insidious  manner  in  which  the  constitutional 
symptoms  are  usually  developed,  and  the  fact  that  some  asthenia 
is  often  present  for  months  before  the  languor  and  weakness 
become  sufficiently  marked  to  be  complained  of,  have  obviously  a 
very  important  bearing  on  this  point.  Probably  the  statement 
which  Dr  Pye-Smith  makes  in  the  second  edition  of  Hilton  Fagge's 
great  work,*  is  as  precise  a  statement  as  it  is  possible  to  make  with 
regard  to  the  period  at  which  the  pigmentation  is  developed.  He 
says  :  "  The  skin  is  always  darker  when  the  symptoms  of  Addison's 
disease  have  lasted  more  than  a  year." 

The  discoloration  is  in  many  cases  so  marked,  that,  even  in  the 
earlier  stages  of  the  case,  it  may  at  once  be  noticed  by  persons  with 
whom  the  patient  is  brought  in  contact.  Thus,  in  a  case  reported 
by  Dr  Henry  Davy,  "  the  patient,  a  male,  aged  25,  obtained  employ- 
ment as  a  baker,  but  after  he  had  continued  his  employment  for  a 
few  months,  he  was  dismissed  by  his  master  on  account  of  his 
'dirty  appearance,'  for  the  discoloration  had  by  this  time  so  in- 
creased that  his  hands,  arms,  and  face  were  quite  '  dark  coloured.'  "f 
In  another  case,  reported  by  Dr  Langdon  Down,|  it  is  stated  that 
"  the  patient's  master  noticed  that  his  face  was  very  dark  when  he 
engaged  him,  but  the  man  replied  that  he  had  been  helping  his 
brother  painting  a  greenhouse,  and  had  got  sunburnt.  The  indoor 
life,  however,  did  not  diminish  the  discoloration  ;  on  the  contrary,  it 
rapidly  increased,  and  his  fellow-servants  gave  him  the  name  of 
'  The  Missionary.' " 

As  regards  its  extent,  depth,  and  colour,  the  pigmentation  varies 
very  considerably  in  different  cases. 

In  some  rare  and  quite  exceptional  cases,  the  pigmentation,  as 
has  been  previously  stated,  is  entirely  absent. 

In  a  small  proportion  of  cases  of  the  disease,  the  discoloration 
is  so  limited  in  distribution  that  it  may  easily  escape  notice  unless 
very  carefully  looked  for.  More  than  one  case  of  this  kind  has 
come  under  my  notice  (see  Cases  II.,  III.,  and  XL). 

The  lesson  which  Case  III.  taught  me,  viz.,  that  in  cases  of  pro- 
found and  apparently  causeless  asthenia,  the  whole  surface  of  the 
skin,  and  especially  the  buccal  mucous  membrane,  should  be  carefully 
examined  in  a  good  light,  since  the  asthenia  may  be  due  to  Addi- 


*  "  Practice  of  Medicine,"  2nd  edition,  Vol.  ii.,  p.  736. 

t  "Transactions  of  the  Pathological  Society  of  London,"  1882,  p.  360. 

\  Ibid,  1869,  p.  389. 


224  DISEASES   OF   THE   BLOOD    GLANDS. 

son's  disease,  has  since  proved  valuable.  I  would  particularly 
emphasise  the  fact  that  in  this  case,  and  also  in  Case  II.,  rapid 
and  extreme  emaciation  and  loss  of  weight  were  very  prominent 
features.  In  Case  III.  the  patient  had  lost  3  st.  in  six  months  ; 
and  in  Case  II.,  4  st.  in  nine  weeks. 

In  the  majority  of  cases  in  which  the  asthenia  and  other  symptoms 
have  lasted  for  any  length  of  time,  the  discoloration  of  the  skin 
is  marked  and  extensively  distributed  over  the  body.  It  may  be 
diffused,  though  by  no  means  equally  so,  over  the  whole  surface  of 
the  body.  In  some  cases,  the  whole  skin  is  so  deeply  pigmented 
that  the  patient,  originally  of  fair  complexion,  comes  to  resemble 
one  of  the  darker  races.  In  a  case  reported  by  Merkel,  the  patient, 
who  used  during  his  illness  frequently  to  come  to  the  hospital,  was 
known  to  the  inmates  of  the  institution  by  the  nickname  of  "Turko."* 
In  the  case  which  is  represented  in  Plate  VI.  of  my  Atlas,  the  skin, 
which  was  originally  white  and  fair,  became  as  black  as  that  of  a 
negro.  The  clinical  features  of  that  case  (Case  I.),  which  is  a  highly 
typical  and  characteristic  one,  are  fully  detailed  below. 

The  pigmented  patches  are  rarely,  if  ever,  abruptly  defined,  as 
the  dark  portions  of  the  skin  in  leucoderma  are ;  in  Addison's 
disease,  the  pigmented  portions,  and  the  more  deeply  pigmented 
patches  in  those  cases  in  which  the  whole  skin  is  discoloured, 
merge  insensibly  into  the  surrounding  skin. 

The  discoloration  is  usually  most  marked — (1)  in  those  situa- 
tions which  are  exposed  to  the  atmosphere,  such  as  the  face  and 
back  of  the  hands  ;  (2)  in  those  parts  of  the  skin  (such  as  the 
areolae  of  the  nipples,  the  genital  organs  in  the  male,  the  perineum, 
the  sides  of  the  axilla,  the  groins,  and  the  skin  around  the  umbilicus) 
in  which  there  is  normally  most  pigment ;  and  (3)  in  those  parts 
of  the  skin  which  are  exposed  to  friction  or  irritation  of  any  kind. 

In  well-marked  cases  of  Addison's  disease,  the  areola;  of  the 
nipples  are  usually  very  deeply  stained  ;  in  the  case  which  is  repre- 
sented in  my  Atlas,  Plates  VI.  and  VII.,  the  nipples  and  their  areolae 
were  as  dark  as  in  a  pregnant  woman.  But  this  is  not  invariable,  even 
in  those  cases  in  which  the  pigmentation  is  extensive.  Two  well- 
marked  cases  have  come  under  my  own  notice  in  which  the  pigmen- 
tation was  very  marked  over  almost  the  whole  body,  but  in  which 
the  nipples  and  their  areolae  were  not  specially  dark-coloured  ;  and 
many  similar  instances  are  to  be  found  amongst  the  recorded  cases. 
Nevertheless,  as  Dr  Greenhow  has  pointed  out,  deep  pigmentation 
of  the  areolne  of  the  nipples  is  very  generally  present,  and  is  of  con- 

*  "  Ziemssen's  Cyclopedia,"  Vol.  viii.,  p.  648. 


ADDISON'S   DISEASE.  225 

siderable  diagnostic  importance  in  distinguishing  the  discoloration 
of  Addison's  disease  from  some  other  forms  of  skin  pigmentation. 
The  same  writer  lays  great  stress  upon  the  presence  of  "  small, 
well-defined  black  specks,  like  black  freckles  or  moles,  on  already 
discoloured  portions  of  skin,"  as  indicating  that  the  discoloration  is 
due  to  Addison's  disease.  In  Plate  X.  of  Addison's  memoir,  in 
which  the  appearance  of  the  skin  in  a  case  of  cancer  of  the  stomach 
with  secondary  deposits  in  the  renal  vein,  and  apoplectic  destruction 
of  the  left  suprarenal  capsule  are  represented,  these  small  deeply 
pigmented  spots  are  well  seen.  Sir  Samuel  Wilks  and  many  other 
authorities  have  denied  that  this  was  a  case  of  Addison's  disease. 
It  must,  however,  be  admitted,  that  if  the  Plate  accurately  repre- 
sents the  appearance  of  the  patient,  the  discoloration  of  the  skin 
was  very  remarkable,  and  unlike  anything  which  is  usually  seen  in 
cancer. 

The  penis  and  scrotum  are  usually  deeply  pigmented  ;  in  a  case 
recorded  by  Dr  Welford,  the  discoloration  of  the  genital  organs 
was  so  extreme  (after  death)  that  the  friends  asked  if  the  parts 
were  not  mortified. 

Parts  of  the  skin  which  have  been  subjected  to  friction  or 
irritation  are  apt  to  become  very  deeply  pigmented.  Portions  of 
skin  to  which  blisters  have  been  applied  are  usually  very  deeply  pig- 
mented, but  this  is  only  an  exaggeration  of  what  takes  place  in  many 
perfectly  healthy  persons.  Deeply  stained  bands  have  in  some  cases 
been  met  with  above  the  knee,  due  to  the  pressure  of  garters,  and 
around  the  waist  in  women,  due  to  the  pressure  of  petticoat-strings 
and  clothes  ;  and  in  one  case  (the  patient  was  a  baker's  boy)  the 
shoulders  were  marked  with  dark  stripes,  corresponding  in  position 
to  the  parts  which  had  been  pressed  upon  by  the  bands  by  which  a 
heavy  basket  was  slung  on  the  patient's  back. 

The  skin  over  the  vertebral  spines  is  apt,  as  the  result  of  the 
pressure  and  irritation  to  which  it  is  subjected  (more  especially 
when  the  patient  is  thin,  and  confined  to  bed  for  any  length  of 
time),  to  become  deeply  stained ;  and  in  rare  cases,  of  which 
III.  and  XL  are  examples,  this  is  the  only  part  of  the  skin  which 
is  pigmented.  This  point  should  be  remembered,  for  it  may  be  of 
great  diagnostic  significance. 

Superficial  cicatrices  and  portions  of  the  skin  which  have  been 
the  seat  of  superficial  eruptions  are  usually  deeply  stained ;  whereas, 
according  to  Dr  Greenhow,  the  cicatrices  of  deeper  injuries  usually 
remain  pale  and  white.  In  the  case  which  is  represented  in  my 
Atlas,  Plate  VI.,  the  lupoid-like  patches,  which  were  situated  on 
the  lower  part  of  the  abdomen,  were  almost  black ;  and  in  Case  IV., 

P 


226  DISEASES   OF   THE    BLOOD   GLANDS. 

in  which  very  marked  improvement  resulted  from  feeding  with 
suprarenal  extract,  the  pitmarks  left  by  a  previous  attack  of  small- 
pox were  much  more  deeply  pigmented  than  the  surrounding 
portions  of  the  skin  of  the  face. 

The  exact  tint  or  shade  of  the  discoloration  varies  in  different 
cases;  brown,  or  some  mixture  of  brown,  is  usually  the  predominant 
tint ;  the  discoloration  which  is  produced  by  staining  the  skin  with 
walnut  juice  exactly  represents  the  colour  in  many  cases  of  Addi- 
son's disease.  The  following  are  some  of  the  terms  in  which  the 
discoloration  has  been  described :  "  dingy,"  "  dusky."  "  smoky," 
"various  shades  or  tints  of  deep  amber  or  chestnut  brown,"  "dirty 
brown,"  "yellowish  brown,"  "greenish  yellow,"  "dark  brown,"  "deep 
bronze,"  "  almost  black,"  "  mulatto-coloured,"  etc. 

In  some  cases,  it  is  stated  that  the  hair  and  iris  shared  in  the 
discoloration,  and  became  darker  as  the  disease  advanced. 

The  nails  are  very  rarely  pigmented.  I  only  know  of  two 
cases  in  which  the  nails  were  discoloured.  In  the  first,  a  very 
remarkable  case,  reported  by  Dr  Finny,*  which  seems  undoubtedly, 
so  far  as  one  can  judge  from  the  symptoms,  to  have  been  a  case  of 
Addison's  disease,  "  the  nails  of  both  hands  and  of  a  few  of  the 
toes  were  stained  ;  in  many,  the  pigment  was  along  the  free  border, 
and  also  over  the  body,  a  space  one-eighth  of  an  inch  in  which  no 
staining  existed  separating  them.  Again,  in  some  the  pigment 
was  laid  down  in  longitudinal  streaks  of  a  black  colour,  the  lunulas 
of  several  being  discoloured  equally  with  the  body  of  the  nail. 
The  pigmentation  of  the  nails  and  fingers  are  such  that  the  more 
observant  would  be  at  once  struck  by  it."  In  the  second  case, 
which  is  reported  by  Drs  Alezais  and  Arnaud.f  and  which  was  in 
every  way  typical,  the  pigmentation  was  very  marked  over  the 
whole  body,  the  discoloration  being  especially  deep  on  the  face, 
scrotum,  penis,  and  the  lunulce  of  the  nails ;  pigmented  patches 
were  also  present  on  the  buccal  mucous  membrane. 
In  one  case,  the  teeth  were,  it  is  said,  discoloured.^ 
In  some  cases,  the  discoloration  of  the  skin  seems  to  vary  in 
intensity  and  depth  from  time  to  time.  In  one  of  my  cases  (Case 
I.)  the  discoloration  of  the  face  and  hands  was  said  to  become 
distinctly  darker  during  the  menstrual  periods. 

Even  in  those  cases  in  which  the  discoloration  is  very  marked, 


*  "  Dublin  Medical  Journal,"  1882,  p.  293. 
+  "Revue  de  Mc-decine,"  10th  April  1891,  p.  296. 

\  Case  34  in  Jaccoud's  list  of  cases,  reported  by  Gromier,  "  Gaz.  Medec." 
Lyon,  1857. 


ADDISON'S   DISEASE.  227 

the  skin  usually  retains  its  normal  softness,  elasticity,  and  pliability  ; 
it  does  not  become  rough  and  wrinkled,  shrivelled,  or  dry.  Excep- 
tions to  this,  as  to  almost  every  other  general  statement  connected 
with  the  disease,  do.  however,  occasionally  occur.  In  a  case  reported 
by  Dr  Bristowe,  "  the  surface  of  the  skin  was  neither  dry  nor  moist, 
but  was  covered  with  a  very  fine  scurf."  *  In  the  case  depicted  in 
Plate  VI.  of  my  Atlas,  the  scalp  was  thickly  coated  with  furfura- 
ceous  scales  ;  and,  at  the  time  when  the  drawing  was  made,  although 
the  skin  of  the  body  generally  was  beautifully  silky,  soft,  and 
pliable,  there  were  one  or  two  slightly  rough  patches  on  the  face. 

Eczematous  and  other  skin  eruptions  have  occasionally  been 
noted  ;  patches  of  leucoderma  are  by  no  means  very  unfrequent ; 
in  one  of  my  cases  (Case  I.)  several  lupoid-like  patches  were 
present  on  the  lower  part  of  the  abdomen  and  one  in  the  left  groin. 

Pigmentation  of  the  Mucous  Membranes. — Deposits  of 
pigment  on  the  lips,  gums,  buccal  mucous  membrane,  tongue,  and 
palate  are  of  frequent  occurrence,  and  are  of  the  greatest  diagnostic 
value. 

On  the  lips,  gums,  and  tongue,  the  pigmented  patches  are 
usually  of  a  bluish-black  colour ;  in  tint  they  closely  resemble 
ink-stains  or  stains  produced  by  blackberry  juice.  On  the  buccal 
mucous  membrane  the  pigmented  patches  are  usually  (always  in 
my  experience)  of  a  dirty  brown  tint,  but  in  some  cases  they  are 
bluish-black,  or  almost  black. 

On  the  lips,  the  deposits  of  pigment,  which  are  usually  situated 
along  the  line  of  contact  of  the  upper  with  the  lower  lip,  or  near 
the  junction  of  the  mucous  membrane  and  of  the  outer  skin, 
generally  take  the  form  of  bluish  black  streaks  running  longi- 
tudinally. In  some  cases  the  lips  have  been  so  deeply  stained  as 
at  first  sight  to  suggest  sordes. 

On  the  gums,  the  pigmentation  usually  occupies  very  much  the 
same  position  as  it  does  in  lead-poisoning  ;  and,  in  fact,  the  dis- 
coloration of  the  gums,  due  to  Addison's  disease,  has  actually 
been  mistaken  for  that  due  to  plumbism.  In  some  cases,  the 
pigmentation  infiltrated  the  gum  tissue  below  the  free  margin 
(Case  VI.). 

On  the  buccal  mucous  membrane,  the  pigmented  deposits  are 
most  frequently  met  with  about  the  angle  of  the  mouth,  and  on  the 
inner  side  of  the  cheek  opposite  the  line  of  junction  of  the  closed 
teeth.  As  Dr  Greenhow  has  pointed  out,  the  localisation  of  the 
pigmented  deposits  on  the  buccal  mucous  membrane  appears  in 


*  "Addison's  Disease,"  by  Dr  Greenhow,  p.  132. 


228  DISEASES   OF   THE   BLOOD   GLANDS. 

some  cases  to  be  determined  by  the  irritation  of  rough,  sharp,  or 
projecting  teeth. 

On  the  tongue  the  pigmented  patches  are  usually  situated  near 
the  free  margin  of  the  organ  ;  but  in  the  case  represented  in  my 
Atlas,  Plates  VI.  and  VII.,  in  which  the  pigmentation  of  the 
tongue  was  unusually  well  marked,  the  deposits  were  chiefly  situated 
on  the  dorsum,  and  especially  about  the  root.  In  that  case,  too, 
several  small,  round,  ball-like  collections  of  pigment  were  present 
under  the  tongue,  on  each  side  of,  and  apparently  adhering  to, 
the  lingual  arteries.  Such  a  condition  has,  so  far  as  I  know, 
not  been  previously  observed  in  the  disease.  It  is  also  present 
in  another  case  which  I  have  at  present  under  observation  (see 
Case  VI.). 

Deposits  of  pigment  may  also  occur  in  other  parts  of  the  body, 
such  as  the  nyniphce,  the  labia  majora  and  minora*  the  vagina^ 
and  the  upper  part  of  the  oesophagus.  In  a  few  cases  (but  whether 
the  staining  in  these  situations  was  actually  the  result  of  the  lesion 
of  the  capsules  has  been  doubted)  deposits  of  pigment  have  been 
found  after  death  in  t\\e  peritoneum  and  pleura,  t 

Anaemia. — Addison,  in  the  passages  which  I  have  quoted,  and 
in  other  parts  of  his  memoir,  lays  great  stress  on  anaemia  as  a 
symptom  of  the  disease.  In  this  he  differs  from  Sir  Samuel  Wilks, 
who  states  positively  that  anaemia  is  not  present.  Sir  Samuel 
Wilks  says  : — "An  opinion  has  prevailed  amongst  many  who  have 
had  no  experience  of  the  complaint,  that  the  constitutional 
symptoms  of  Addison's  disease  are  characterised  by  ansemia  and 
wasting.  This  is  not  the  case,  as  neither  of  these  conditions  is 
present."  § 

Now,  at  the  first  glance,  a  patient  affected  with  typical  Addi- 
son's disease  certainly  does  look  profoundly  anaemic  ;  the  remark- 
ably pale,  pearly  conjunctiva — "  the  ancsmiated  eye','  as  Addison 
himself  termed  it — contrasting  so  forcibly  as  it  does  with  the  dark 
hue  of  the  face,  is  highly  suggestive  of  marked  anaemia  ;  but  in 
most  cases  of  the  disease — and  this  is  a  very  striking  feature  of  the 


*  See  cases  by  Drs  Haclden  and  Seymour  Taylor,  "Path.  Soc.  Trans.,"  1885. 
pp.  435  and  449. 

t  Dr  Dixon  Mann's  case,  "Lancet",  21st  March  1891,  p.  653. 

%  See  Dr  Hadden's  case,  "Path.  Soc.  Trans.",  1885,  p.  436.     Also  case  21  in 
Sir  Samuel  Wilks'  series  ;  in  this  case  specks  of  pigment  of  a  dark  colour  were 
present  in  the  omentum  and  peritoneum,  and  on  the  surface  of  the  ovaries  and 
mucous  membrane  of  the  stomach,  near  the  pylorus. — "Guy's  Hospital  Reports, 
vol.  viii.  (1862). 

i  Russell  Reynold's  "System  of  Medicine,"  vol.  v.,  p.  357. 


ADDISON'S   DISEASE.  229 

case  which  is  represented  in  my  Atlas,  Plate  VI. — the  lips,  gums, 
and  tongue  are  well,  indeed  it  may  be  deeply,  coloured. 

But  although  a  high  degree  of  bloodlessness  is  rarely  met  with, 
I  cannot  help  thinking  that  a  moderate  degree  of  anaemia,  as 
estimated  by  the  number  of  red  blood  corpuscles,  is  not  unfrequently 
present.  In  a  typical  case  reported  by  Greenhow,  the  patient  is 
stated  to  have  been  "  remarkably  anaemic,  the  lining  membrane  of 
the  eyelids,  the  lips,  tongue,  and  gums  being  pale  and  bloodless."  * 
In  at  least  three  of  the  cases  which  have  come  under  my  own 
observation,  the  buccal  mucous  membrane  covering  the  inside 
of  the  cheeks,  the  conjunctiva  covering  the  lower  lid  as  well  as 
that  covering  the  eyeball  itself,  and  the  nails,  were  paler  than 
normal.  In  one  case  (Case  I.),  for  example,  the  red  corpuscles 
numbered  3,250,000  as  compared  with  4,500,000,  which  may  be 
taken  as  the  average  standard  of  health  in  the  female;  while  the 
haemoglobin  as  estimated  by  Gowers'  instrument  equalled  80  per 
cent.  The  condition  of  the  blood  in  this  case — some  diminu- 
tion of  the  red  blood  corpuscles,  but  no  diminution  of  the  haemo- 
globin— has  been  present  in  some  other  cases  which  I  have  examined. 
In  another  case  which  came  under  my  notice  a  few  years  ago  (the 
patient  was  a  male),  the  red  blood  corpuscles  numbered  3,500,000 
per  cubic  millimetre. 

Now,  as  I  have  previously  pointed  out  (see  p.  16),  80  per  cent, 
of  haemoglobin,  as  estimated  by  Gowers'  instrument,  is,  in  my 
experience,  little  if  at  all  short  of  the  average  standard  of  health. 
But  whether  this  be  allowed  or  not,  it  is  certain  that  the  corpuscular 
richness  in  haemoglobin  (the  percentage  of  haemoglobin  in  each 
individual  red  blood  corpuscle),  was,  in  this  case,  at  least  equal  to 
the  normal.  Such  a  condition  of  the  blood  is  very  different  from 
that  in  chlorosis.  It  is  hardly  necessary  to  add  that  the  com- 
paratively slight  diminution  in  the  number  of  the  red  blood 
corpuscles  at  once  distinguishes  the  anaemia  of  Addison's  disease 
(granting  that  some  anaemia  is  often  present)  from  the  idiopathic 
anaemia  of  Addison — progressive  pernicious  anaemia,  as  it  is  now 
termed  ;  though  in  some  cases  of  Addison's  disease,  as  in  pernicious 
anaemia,  the  colour  index  may  be  above  the  normal. 

On  microscopical  examination  the  red  corpuscles  are  usually 
normal  in  size  and  shape.  In  some  cases,  a  slight  excess  of  white 
corpuscles  is  present ;  but,  so  far  as  my  experience  enables  me  to 
judge,  this  is  inconstant.  Buhl  and  Laschkewitsch  (quoted  by 
Merkel  f )   lay  stress   upon    the    absence    of  the    tendency  of  the 

*  "  Addison's  Disease,"  p.  101.       t  Ziemssen's  "  Cyclopaedia,"  vol.  viii.,  p.  655. 


230  DISEASES   OF   THE   BLOOD   GLANDS. 

blood  corpuscles  to  form  rouleaux.  I  have  not  observed  this  in 
any  of  the  cases  I  have  examined  ;  and  Dr  Greenhow's  opinion  on 
this  point  coincides  with  mine,  for  he  states  that  in  the  cases  which 
he  examined  microscopically  the  blood  appeared  to  be  normal. 

In  one  or  two  cases  free  pigment  granules  have  been  described 
in  the  blood,  but  confirmation  of  the  fact  is  required  before  any  im- 
portance can  be  attached  to  their  presence.  In  none  of  the  cases 
which  I  have  examined  were  pigmented  particles  present. 

Nervous  Symptoms. — During  the  course  of  Addison's  disease 
various  nervous  symptoms  are  apt  to  occur.  In  addition  to  the 
pains  in  the  abdomen  and  back,  and  the  paroxysmal  attacks  of 
( ?  nervous)  vomiting,  diarrhoea,  and  cardiac  debility,  which  have 
already  been  described,  headache,  vertigo,  temporary  dimness  of 
vision,  flashes  of  light  before  the  eyes,  noises  in  the  ears,  temporary 
deafness,  are  of  frequent  occurrence. 

Numbness,  anaesthesia,  and  hyperaesthesia  are  occasionally, 
though  rarely,  met  with.  Merkel  states  that  he  has  observed 
severe  pains  in  the  joints,  which  resembled  in  character  the  arthritic 
neuroses  of  hysterical  patients  ;  these  pains  were  unaccompanied 
by  swelling,  and  were  not  increased  by  direct  pressure  over  the 
joints. 

An  excessive  tendency  to  sleep  occurs  in  some  cases ;  in  others, 
more  especially  during  the  paroxysmal  exacerbations,  and  par- 
ticularly during  the  periods  of  depression  in  the  later  stages  of  the 
disease,  that  form  of  restlessness  and  sleeplessness,  which  is  so 
frequently  associated  with  profound  exhaustion  and  anaemia,  may 
be  a  prominent  symptom. 

Rigors,  subsultus  tendinum,  choreic-like  twitchings,  and  general 
or  localised  epileptiform  convulsions  (which  sometimes  occur  in  the 
earlier  stages  of  the  disease),  are  not  unfrequent  before  death ;  in 
fact,  in  several  of  the  reported  cases,  the  patient  has  died  in  an 
epileptic  fit. 

The  intellectual  faculties  usually  remain  unaffected,  at  all  events 
until  the  later  stages  of  the  case.  Before  death,  the  patient  often 
passes  into  a  listless,  torpid,  or  "  typhoid  "  state  ;  stupor,  delirium, 
or  coma  frequently  occur  during  the  last  few  hours  or  days  of  life. 
When  these  symptoms  are  developed,  the  end  is  usually  near  at 
hand  ;  but  this  is  not  always  so.  In  a  remarkable  case,  which  was 
under  the  care  of  Dr  Burdon  Sanderson,  "  the  patient  remained  for 
several  days  in  a  state  of  noisy,  talkative  delirium,  frequently 
endeavouring  to  get  out  of  bed,  making  grimaces,  singing,  vociferat- 
ing rapidly  and  incoherently,  or  shrieking  out  as  if  in  terror." 
She,  however,  recovered   from  this  condition  (which  was  perhaps 


ADDISON  S   DISEASE.  231 

hysterical),  and  died  nearly  a  year  afterwards  from  the  disease, 
death  being  preceded  by  an  epileptic  fit.*  The  question  naturally 
occurs  whether  the  delirium  in  this  case  was  not  hysterical. 

Some  of  the  nervous  symptoms,  such  as  pains  in  the  back  and 
abdomen  and  paroxysmal  attacks  of  nervous  vomiting,  are  due  to 
implication  of  the  suprarenal  nerves  or  branches  of  the  solar  plexus. 
Others,  such  as  numbness  or  anaesthesia  in  the  legs,  are  perhaps  the 
result  of  lesions  of  the  spinal  cord — for  such  lesions  have  been 
described  in  some  cases  of  the  disease. 

The  Temperature  in  Addison's  disease  is  usually  normal  or 
subnormal.  Absence  of  febrile  disturbance  is  one  of  the  character- 
istic (negative)  signs  of  the  disease. 

Patients  affected  with  Addison's  disease  usually  bear  both  heat 
and  cold,  but  especially  cold,  badly ;  as  I  have  previously  pointed 
out,  their  vasomotor  nerve  tone  and  resisting  power  are  seriously 
enfeebled.  They  require  to  be  carefully  protected  from  cold,  and 
from  all  the  vicissitudes  of  the  weather. 

The  state  of  Nutrition. — The  absence  of  any  marked  degree 
of  emaciation  is  an  important  feature  of  most  uncomplicated  cases 
of  Addison's  disease.  In  the  earlier  stages,  there  may  be  absolutely 
no  loss  of  flesh,  and  this  even  when  the  asthenia  is  very  pronounced. 
As  the  case  goes  on,  the  patient  does,  as  a  rule,  lose  weight,  the 
muscles,  as  one  might  naturally  expect,  becoming  soft,  flabby,  and 
more  or  less  atrophied.  But  in  uncomplicated  cases  the  body 
usually  remains  well  covered  with  fat  even  up  to  the  time  of  death. 
In  many  of  the  recorded  cases,  in  which  emaciation  was  said  to 
have  been  present  during  life,  a  considerable  layer  of  fat  was,  on 
post-mortem  examination,  found  in  the  front  wall  of  the  abdomen, 
and  over  the  body  generally. 

The  very  striking  atrophy  which  is  in  some  cases  met  with  in 
the  heart  has  already  been  alluded  to. 

The  absence  of  emaciation,  so  far  as  the  fat  is  concerned,  is  not. 
however,  as  some  writers  have  stated,  an  invariable  characteristic 
of  Addison's  disease.  Some  exceptional  cases  have  been  recorded, 
and  Cases  II.  and  III.  are  excellent  illustrations,  in  which  consider- 
able emaciation  was  present,  even  in  uncomplicated  cases.  Distaste 
for  food,  and  unusually  severe  and  long-continued  vomiting,  were, 
perhaps,  the  causes  of  the  emaciation  in  some  cases  of  this  kind  ;  but 
this  is  certainly  not  always  so.  When  the  lesion  of  the  capsules  is 
complicated  by  extensive  phthisis,  active  caries  of  the  spine,  or,  as 
it  sometimes  is,  with  suppuration  (psoas  abscess,  etc.),  and  with 

*  "  Transactions  of  the  Pathological  Society  of  London,"  Vol.  xx.,  p.  378. 


232  DISEASES   OF   THE   BLOOD   GLANDS. 

hectic  fever,  marked  emaciation  may  of  course  be  present ;  but  even 
when  complicated  with  lesions  of  this  kind,  there  is  seldom,  if  ever, 
in  Addison's  disease,  the  extreme  emaciation  and  the  dry  withered 
appearance  which  are  characteristic  of  the  cachexia  of  advanced 
malignant  disease. 

In  some  cases  emaciation,  more  especially  wasting  of  the  muscles, 
seems  to  be  part  and  parcel  of  the  disease.  In  Addison's  original 
description,  wasting  is  mentioned  as  a  feature  of  the  disease. 

Dr  Greenhow  used  to  lay  great  stress  upon  the  absence  of 
emaciation  ;  indeed,  in  one  case  about  which  I  consulted  him  some 
twenty  years  ago,  he  went  so  far  as  to  say  that  the  fact  that  the 
patient  was  emaciated  negatived  the  view  of  Addison's  disease. 

Now,  while  I  admit  that  in  most  cases  of  Addison's  disease, 
there  is  no  emaciation — at  all  events  so  far  as  the  body  fat  is  con- 
cerned— I  know,  from  cases  which  have  come  under  my  own 
observation,  that  most  marked  and  rapid  emaciation,  without  any 
associated  visceral  disease  to  account  for  it,  is  in  some  cases 
developed.  I  believe  that  in  the  great  majority  of  cases  of  Addi- 
son's disease  the  muscles,  including  the  heart  muscle,  become 
atrophied;  indeed,  as  I  have  stated,  I  am  disposed  to  think  that 
the  atrophy  of  the  heart  muscle  is  one  of  the  most  important 
clinical  and  pathological  facts  connected  with  the  disease.  In 
one  of  my  cases  (Case  II.)  the  patient  lost  no  less  than  4  stones 
in  weight  in  a  period  of  nine  weeks.  I  am  disposed  to  think  that 
this  great  loss  of  weight  was  chiefly  due  to  the  disease  of  the  supra- 
renal capsules  ;  it  can  hardly,  I  think,  be  satisfactorily  accounted 
for  by  the  very  recent  deposit  of  tubercle,  with  practically  speaking 
little  or  no  peritonitis,  which  was  found  in  the  peritoneum  after 
death.  In  another  case  (Case  III.),  the  patient  lost  3  st.  in  weight 
during  a  period  of  six  months  ;  and  it  was  the  recollection  of  the 
facts  of  Case  III.  which  led  me,  after  I  had  excluded  some  of  the 
conditions  which  are  more  common  causes  of  asthenia  and  emacia- 
tion, to  look  for  the  symptoms  of  Addison's  disease  in  Case  II. 
I  repeat,  that  in  some  (exceptional)  cases  of  Addison's  disease  there 
is  marked  and  rapid  loss  of  weight  and  flesh. 

The  urine  in  Addison's  disease  does  not  as  a  rule  present  any 
striking  or  characteristic  change.  The  daily  amount  is  sometimes 
less,  sometimes  greater,  than  the  normal  ;  the  specific  gravity  is 
usually  low.  The  amount  of  urea  per  diem  is  usually  considerably 
below  the  normal,  but  this  is  partly  at  least  accounted  for  by  the 
small  amount  of  food,  and  the  kind  of  food,  which  the  patient  takes  ; 
there  seems  good  reason,  however,  for  supposing  that  in  Addison's 
disease  the  tissue  metabolism  is  below  the  normal  standard. 


ADDISON'S   DISEASE.  233 

In  a  few  of  the  recorded  cases,  an  excess  of  indican  has,  it  is 
said,  been  present  in  the  urine,  but  this  seems  exceptional.  In  a 
case  which  came  under  my  notice  a  few  years  ago,  but  in  which  I 
had  no  opportunity  of  making  a  detailed  analysis  of  the  urine,  the 
addition  of  nitric  acid  produced  an  exceedingly  dark  discoloration 
of  the  urine.  In  the  case  which  is  reproduced  in  Plate  VI.  in  my 
Atlas  of  Clinical  Medicine,  in  which  the  pigmentation  of  the  skin 
was  extremely  marked,  the  urinary  pigments  were  by  no  means 
increased — in  fact,  rather  the  reverse.  Dr  William  Hunter  kindly 
made  an  analysis  for  me  of  the  urinary  pigments  in  this  case. 

In  a  small  number  of  the  reported  cases  of  Addison's  disease, 
albumen,  pus,  or  other  abnormal  constituents  have  been  present  in 
the  urine ;  but  their  occurrence  was  clearly  accidental,  and  due  to 
some  complicating  condition. 

Non-development  or  atrophy  of  the  genital  organs  and  of 
the  mammae. — In  a  case,  that  of  a  man  aged  twenty-nine,  which  I 
examined  post  mortem  a  few  years  ago,  the  genital  organs  were 
completely  undeveloped,  the  testicles  being  no  larger  than  small 
filberts.  The  same  fact  has  been  recorded  in  a  few  other  cases. 
In  the  case  of  a  girl,  aged  eighteen,  reported  by  Dr  Dixon  Mann, 
"  the  uterus  was  infantile,  and  the  external  genitals  like  those  of  a 
young  child  ;  the  ovaries  were  small,  and  showed  one  or  two 
cicatrices,  but  not  of  recent  origin."  * 

The  mammae  are  not  unfrequently  much  atrophied  in  the  later 
stages  of  the  disease,  but  this  is  certainly  not  always  so,  even  in  very 
long  standing  cases  (see  Case  I.). 

The  menstruation  is  usually  irregular  or  entirely  suppressed. 
In  one  of  my  own  cases  (Case  XI.)  there  was  dysmenorrhcea  and 
menorrhagia. 

Foetid  odour  of  the  body. — In  a  few  of  the  recorded  cases  a 
foetid  odour,  said  sometimes  to  resemble  the  odour  given  off  from 
the  bodies  of  the  darker  races  of  mankind,  has  been  observed.  In 
some  cases,  especially  towards  the  termination  and  shortly  before 
death,  a  cadaveric  smell  has  been  exhaled  from  the  body  ;  in  others 
the  breath  had  a  heavy,  ethereal,  or  acetone-like  odour. 

The  frequency  of  occurrence  of  the  more  important  symptoms, 
in  my  twelve  cases  of  Addison's  disease,  is  shown  in  Table  7. 

*  "  Lancet,"  21st  March  1891,  p.  653. 


111 

-o4 


DISEASES   OF   THE    BLOOD   GLANDS. 


Table  7. — Showing  the  more  Important  Symptoms  in  Twelve  Cases 
of  Addison's  Disease  observed  by  the  Author  during  Life. 


« 

c 
25 

V 

tat 

< 

5 

26 

< 

i 

F. 

M. 

2 

5° 

M. 

M. 

3 

36 

M. 

M 

4 

37 

M. 

M. 

5 

41 

M. 

M. 

6 

8^ 

F. 

M. 

7 

iS 

F. 

M. 

8 

46 

M. 

.M.J 

*9 

■9 

F. 

M.  | 

10 

49 

M. 

M- 

11 

25 

F. 

M.  1 

1 

12 

45 

M. 

M. 

M.(4st.) 
M.(3st.) 


j£ 

0  H 

Pigmentation. 

u 

c 

'1 
> 

1 

?. 
3 

0 

e 

- 

0 

V    u 
C    C 
—    3 

n'c1 

v  0 

e 

c 
< 

l 

M     & 

ot-'H. 
<     2 

V 

«  3  S3 

8  8-0 

33  = 

1 

1 

M. 

0 

1 

M. 

0 

0 

0 

1 

1 

1 

0 

0 

1 

0 

0 

0 

1 

1 

V.s 

0 

0 

1 

0 

0 

1 

i 

0 

M. 

1 

1 

M. 

0 

1 

1 

1 

1 

M. 

0 

1 

0 

I 

0 

0 

0 

0 

M. 

1 

1 

1 

0 

0 

0 

1 

1 

M. 

0 

0 

M. 

I 

0 

1 

1 

1 

M. 

0 

0 

1 

0 

0 

1 

1 

1 

M. 

1 

7 

0 

'J 

0 

0 

1 

1 

M. 

0 

I 

0 

1 

0 

1 

1 

1 

V  s. 

0 

? 

1 

0 

1 

9 

1 

1 

M. 

•) 

1 

0 

Result. 


Death 
Death 
Death 
Death 

I.s.q. 

? 

? 
Death 

Recovery 
Death 


Total 
Duration. 


13  to  14  year; 
3  years 

6  months 
3  years 
1  year  t 

7  months 
2  years  J 

4  months  t 
2:V  years 
1  j  years  t 
35  years  t 
7  months 


Post  mortem. 


None 

Typical      fibro  -  caseous 

change 
Simple  fibrous  atrophy 

Fatty     transformation     of 
capsules 


Left  capsule  enlarged  and 
caseous  :  right  normal  t 


M  =  Marked.     i  =  Present.    o  =  Absent.     V.s.  =  Very  slight.     I.s.q.  =  In  statu  quo. 

Complicated  with  enlargement  of  glands  ;  itchiness  of  skin  (dermatitis  herpetiformis).        t  Intrathoracic  tumour  ; 
cyst  in  right  frontal  lobe.         {  Before  coming  under  my  observation. 


Complications  and  Associated  Lesions. 

In  many  cases  of  Addison's  disease,  the  case  remains  uncom- 
plicated to  the  end,  and  no  associated  lesions,  except  those  which 
may  easily  be  explained  by  the  disease  itself  (such,  for  example,  as 
the  secondary  lesions  in  the  gastro-intestinal  tract),  are  found  in  the 
body  after  death. 

Tubercular  lesions  in  the  lungs  are  by  far  the  most  common 
complications.  In  many  cases,  these  pulmonary  lesions  are  old, 
clinically  insignificant,  and  incapable  of  being  recognised  during 
life  ;  but  in  a  certain  proportion  of  cases  the  clinical  signs  indicative 
of  more  extensive,  and  it  may  be  actively  progressive  and  wide- 
spread, tubercular  lesions  are  present. 

Active  caries  of  the  spine  and  lumbar  abscesses  have  been  met 
with  in  a  considerable  number  of  cases ;  and  curvature  of  the  spine, 
the  result  of  old  and  cured  spinal  caries,  occasionally  also  occurs. 

Occasionally  extensive  tubercular  deposits  are  developed  in  the 
peritoneum  and  other  parts  of  the  body. 


addison's  disease.  235 

Clinical  Types. 

Different  cases  of  Addison's  disease  present  considerable  differ- 
ences in  respect  to  their  mode  of  development,  duration,  clinical 
history,  and  course  ;  they  may,  I  think,  be  divided  into  the  following 
clinical  types  or  varieties  : — 

(1.)  Typical  and  uncomplicated  cases  of  the  disease. — This 
group  includes  the  great  majority  of  cases.  The  onset  is  insidious, 
and  not  usually  preceded  by  any  apparent  cause  or  illness.  The 
characteristic  symptoms  which  have  been  described  above  in  detail 
(asthenia,  extreme  feebleness  of  the  heart  and  pulse,  vomiting, 
pigmentation,  and  usually  some  anaemia,  and  pain  in  the  abdomen 
and  back)  are  well  marked.  There  is  no  obvious  local  or  visceral 
disease  to  account  for  the  symptoms  and  ill  health.  The  average 
duration  (in  the  case  of  hospital  patients)  is  probably  about  two 
years  after  the  asthenia  and  other  symptoms  have  become  suffi- 
ciently striking  to  attract  the  attention  of  the  patient.  In  most 
cases,  temporary  exacerbations  of  the  symptoms  occur ;  in  others, 
there  are  temporary  periods  of  improvement ;  but  the  course  of  the 
case  is  on  the  whole  progressively  downwards,  and  the  termination, 
with  very  rare  exceptions,  is  in  death. 

(2.)  Atypical  and  exceptional  cases. — This  group  includes  at 
least  two  varieties  of  sub-groups,  viz. : — 

(a.)  Cases  in  which  the  development  of  the  disease  is  (or  appears 
to  be)  rapid,  and  the  duration  short.  Looking  at  the  clinical  features 
of  these  cases,  they  may  not  incorrectly  be  termed  acute.  Dr 
Greenhow  cites  a  number  of  cases  of  this  kind.*  One  well-marked 
case  has  come  under  my  own  notice  (Case  III.). 

(b.)  Cases  in  which  there  is  no  pigmentation,  or  in  which  the  pig- 
mentation is  so  slight  as  to  easily  escape  observation.  Cases  in  which 
the  pigmentation  is  entirely  absent  are  exceedingly  rare,  but  they 
do  undoubtedly  occur. 

Cases  in  which  the  pigmentation  is  so  slight  as  to  escape 
attention,  unless  it  is  carefully  looked  for,  are  more  common. 
Between  these  two  extremes — cases  in  which  the  pigmentation  is 
so  slight  as  to  make  the  case  exceptional,  and  cases  in  which 
the  pigmentation  is  excessively  developed — there  are  all  degrees 
of  variety ;  it  is  only  the  cases  in  which  the  pigmentation  is 
entirely  absent  or  very  sparingly  developed  which  can  be  termed 
exceptional. 

(3.)  Cases  in  which  the  symptoms  of  Addison's  disease  are 

*  "On  Addison's  Disease,"  p.  18. 


236  DISEASES   OF   THE   BLOOD   GLANDS. 

superadded  to  the  symptoms  of  some  other  disease,  such  as 
phthisis. — Clinical  observation  would  seem  to  show  that  cases  of 
this  kind  are  by  no  means  very  rare,  but  the  correctness  of  this 
conclusion  is  not,  so  far  as  my  experience  enables  me  to  judge, 
borne  out  by  examination  after  death,  for  in  several  cases  of  phthisis, 
in  which  the  discoloration  was  so  marked  as  to  suggest  the  presence 
of  Addison's  disease,  the  suprarenal  capsules  were  at  the  post 
mortem  found  to  be  healthy  to  the  naked  eye.  The  diagnosis  (so 
far  as  the  recognition  of  a  lesion  of  the  capsules  is  concerned)  is, 
in  cases  of  this  kind,  attended  with  great  difficulty. 

Pathological  Classification. — I  need  hardly  say  that  this  classi- 
fication is  entirely  clinical.  If  a  pathological  basis  of  classification 
were  adopted,  cases  of  Addison's  disease  might  be  divided  into  the 
following  groups  : — 

(A.)  Typical  cases,  in  which  both  capsules  are  affected,  and 
usually  completely  destroyed,  by  the  fibro-caseous  (tubercular) 
lesion. 

(B.)  Atypical  and  exceptional  cases.  Under  this  head  there 
are  several  sub-groups,  viz. : — 

(a.)  Cases  in  which  one  capsule  only  is  affected  with  the  char- 
acteristic fibro-caseous  (tubercular)  lesion,  the  other  being  sound. 

(b.)  Cases  in  which  both  capsules  have  been  completely  destroyed, 
apparently  by  cirrhotic  or  simple  atrophy. 

(c.)  Cases  in  which  both  capsules  have  apparently  been  replaced 
by  fat. 

(d.)  Cases  in  which  both  capsules  are  congenitally  absent. 

(<?.)  Cases  in  which  the  symptoms  (or  some  of  the  symptoms) 
of  the  disease  are  associated  with  cancerous  destruction  of  the 
capsules. 

And  (/)  cases  in  which  the  symptoms  (or  some  of  the  symptoms) 
of  the  disease  are  associated  with  disease  of  the  abdominal  sym- 
pathetic (as  in  Gowers'  and  Paget's  cases),  the  capsules  themselves 
being  sound. 

Duration. — The  average  duration  of  cases  of  Addison's  disease 
in  hospital  cases  is  probably  about  two  years,  if  we  date  the  dura- 
tion from  the  time  of  appearance  of  the  first  symptoms,  i.e.,  from 
the  time  at  which  the  patient  first  distinctly  complained  of  asthenia, 
or  at  which  the  pigmentation  was  first  noticed. 

A  duration  of  five  or  six  years,  more  especially  amongst  well- 
to-do  patients,  is  probably  not  very  uncommon.  In  the  case  which 
1  have  illustrated  in  Plate  VI.  of  my  Atlas  of  Clinical  Medicine 
(see  Case  I.),  the  patient  lived  for  at  least  nine  years  after  the 
characteristic  symptoms  of  the  disease  were  developed. 


ADDISON'S   DISEASE.  237 

In  some  cases,  the  course  is  much  more  rapid — six  months  to  a 
year  ;  and  a  few  cases  have  been  recorded  in  which  the  duration 
was  said  to  be  only  a  few  weeks.  It  is  probable  that  in  many 
of  the  rapid  cases,  the  lesion  in  the  suprarenal  capsules  was  of  much 
longer  duration  than  the  clinical  duration  of  the  case  would  seem  to 
indicate  ;  for,  as  Sir  Samuel  Wilks  has  pointed  out,  there  is  every 
reason  to  suppose,  from  the  pathological  characters  of  the  capsular 
lesion  found  after  death — the  extensive  caseation  and  calcification 
which  are  found  after  death — that  in  many  cases  the  capsules  have 
been  entirely  destroyed  for  months,  probably  in  some  cases  for 
years,  before  the  symptoms  of  the  disease  become  sufficiently 
prominent  to  attract  attention.  In  the  cases  which  run  a  rapid 
course,  the  pigmentation  is  usually  less  marked  than  in  the  ordi- 
nary typical  (chronic)  cases,  and  in  very  exceptional  instances  may 
indeed  be  altogether  absent. 

Termination. — The  vast  majority  of  cases  of  Addison's  disease 
terminate  sooner  or  later  in  death ;  indeed,  many  writers  deny 
that  the  disease  is  ever  recovered  from.  A  few  cases  have,  how- 
ever, been  reported  in  which  recovery  does  appear  to  have  taken 
place.  In  the  discussion  on  Addison's  disease  at  the  International 
Medical  Congress  of  London,  Sir  William  Gull  mentioned  a  case 
in  which  a  patient,  aged  57,  who  had  presented  all  the  symptoms 
of  the  disease,  had  completely  recovered.*  Dr  Finnyf  has  reported 
a  very  remarkable  case,  in  which  all  the  characteristic  symptoms  of 
the  disease  appear  to  have  been  present,  in  which  there  was  no 
evidence  of  any  local  or  visceral  disease,  and  in  which  complete 
recovery  took  place.  In  a  case  of  my  own,  in  which  there  is, 
I  think,  reason  to  suppose  that  the  patient  was  affected  with  the 
disease,  recovery  has  also  occurred  (see  Case  XI.). 

On  theoretical  grounds,  and  granting  that  the  lesion  is  usually 
tubercular,  there  is  every  reason  for  supposing  that  recovery  may 
occasionally  occur. 

Mode  of  Death. — In  most  cases,  death  is  gradual,  the  result  of 
asthenia  and  gradually  increasing  exhaustion  and  debility  ;  in 
many  cases,  the  patient  sinks,  for  some  days  or  hours  before  death, 
into  a  semi-comatose  or  typhoid  state.  In  some  cases,  death  is 
preceded  by  a  period  of  extreme  restlessness  ;  in  others,  by  deli- 
rium, coma,  a  convulsion,  or  a  series  of  epileptic  fits.  As  we  might 
expect,   sudden   death  sometimes   occurs   as   the  result  of  cardiac 


*  "  Transactions  of  the  International  Medical  Congress  of  London,"  Vol.  ii., 

P-  75- 

t  "Dublin  Medical  Journal,"  1882,  p.  293. 


238  DISEASES   OF   THE   BLOOD   GLANDS. 

syncope.  A  very  striking  case  of  this  kind  (which  shows  the  im- 
portance of  guarding  the  subjects  of  Addison's  disease  from  any 
sudden  excitement  or  effort)  is  reported  by  Dr  Kendal  Franks. 
A  CTirl  aged  14,  affected  with  Addison's  disease,  and  in  whom 
the  asthenia  was  intense,  suddenly  awoke  hearing  the  noise  occa- 
sioned by  a  row  in  the  street  in  front  of  the  hospital ;  she  jumped 
up  in  bed  with  a  shriek  of  terror,  and  immediately  fell  backwards, 
dead.* 

Diagnosis. 

In  some  cases  of  Addison's  disease  the  diagnosis  is  easy,  in 
others  most  difficult,  or  impossible. 

Pigmentation  of  the  skin,  and  especially  pigmentation  of  the 
mucous  membranes,  is,  for  the  purpose  of  diagnosis,  by  far  the  most 
important  symptom,  or  rather  sign,  of  the  disease. 

It  is  perhaps  hardly  necessary  to  say  that  pigmentation  of  the 
skin  per  se  {i.e.,  without  asthenia  and  other  constitutional  symp- 
toms) is  not  sufficient  to  justify  a  diagnosis  of  Addison's  disease. 
The  pigmentation  of  the  skin  in  Addison's  disease  is  in  no  way 
peculiar  ;  it  is  not  pathognomonic  ;  but  it  may,  with  confidence,  be 
stated  that  such  extreme  pigmentation  as  is  present  in  the  case 
represented  in  Plate  VI.  of  my  Atlas  (Case  I.  Illustrative  Cases) 
is  very  rarely  indeed  developed  except  as  the  result  of  Addison's 
disease.  One  case  has,  indeed,  come  under  my  own  notice,  in 
which  very  marked  discoloration  of  the  skin,  identical  in  character 
with  that  of  Addison's  disease,  developed  apparently  as  the  result 
of  chronic  scurvy,  and  independently  of  any  disease  of  the  supra- 
renal capsules  or  the  adjacent  nerves  ;  but  such  cases  are  so  in- 
finitely rare  that  for  the  purposes  of  practical  diagnosis  they  may 
be  safely  ignored.  Sir  Samuel  Wilks  puts  the  value  of  extreme 
pigmentation  very  forcibly,  when  he  says  :  "  I  do  not  know  of  any 
other  disease  which  changes  a  white  man  into  the  appearance  of  a 
black  one."  t 

Pigmentation  of  the  mucous  membranes  may,  however,  for  the 
purposes  of  practical  diagnosis  be  said  to  be  pathognomonic  ;  for 
although  a  few  cases  have  indeed  been  reported — all,  so  far  as  I 
know,  cases  of  phthisis  or  tubercular  disease — in  which  pigmenta- 
tion of  the  buccal  mucous  membranes,  identical  with  that  of 
Addison's  disease,  was  present  during  life,  and  in  which  the 
capsules  were  found,  to  the  naked  eye  at  least,  to  be  healthy  after 


*  "  Dublin  Medical  Journal,"  1882,  p.  279. 

t  "Guy's  Hospital  Reports,"  vol.  viii.,  1862,  p.  14. 


ADDISON'S   DISEASE.  239 

death,  such  cases  are  so  exceedingly  rare  that  for  practical  pur- 
poses they  may  be  left  out  of  account.  Possibly  in  some  of  these 
cases  microscopical  examination  might  have  demonstrated  a  tuber- 
cular lesion  of  the  capsules  ;  but  to  this  point  I  shall  again  refer  in 
speaking  of  the  pathology  of  the  disease. 

In  order  to  warrant  a  positive  diagnosis  of  Addison's  disease 
three  factors  are  necessary,  viz.  : — 

(1.)  The  presence  of  the  characteristic  constitutional  symptoms 
(asthenia,  vomiting,  and  in  most  cases  the  absence  of  marked 
emaciation,  and  the  presence  of  some  anaemia,  and  of  pain  in  the 
abdomen  and  back). 

(2.)  Pigmentation  of  the  skin  (with  the  characters  described 
above),  and,  still  more,  pigmentation  of  the  mucous  membranes. 

(3.)  The  absence  of  any  local  visceral  disease  (other  than  the 
lesion  of  the  suprarenal  capsules)  capable  of  accounting  for  the 
symptoms  (asthenia,  pigmentation,  etc.). 

When  these  three  factors  are  all  present,  a  positive  diagnosis 
may  be  confidently  made.  In  other  words,  the  recognition  of 
typical  cases  of  Addison's  disease  is  no  more  difficult  than  the 
recognition  of  many  other  well-marked  clinical  entities. 

It  is  the  atypical  and  complicated  cases  in  which  the  diagnosis 
is  difficult  or  impossible. 

The  diagnosis  of  the  atypical  cases  in  which  there  is  little 
or  no  pigmentation.- — In  cases  of  this  kind  the  diagnosis  is  most 
difficult  ;  in  fact,  in  the  absence  of  pigmentation,  although  the 
presence  of  Addison's  disease  may  be  suspected,  a  positive  diagnosis 
is  rarely  possible. 

We  may  strongly  suspect  the  presence  of  Addison's  disease 
when  marked  and  progressive  asthenia,  unassociated  with  emacia- 
tion and  without  fever,  develops  without  any  apparent  cause.  The 
suspicion  is  strengthened  if  the  patient  is  young  (in  other  words, 
in  cases  in  which  obscure  internal  disease  of  a  malignant  kind  is 
not  likely  to  occur),  if  there  is  no  profound  anaemia,  and  if  symp- 
toms of  gastro-intestinal  irritation  (which  seem  to  be  of  nervous 
origin,  and  which  do  not  appear  to  be  due  to  local  stomach 
disease,  such  as  simple  ulceration)  and  lumbar  pains  are  also 
present.  Further,  it  must  be  remembered  that  marked  loss  of 
weight  does  not  exclude  Addison's  disease. 

In  cases  of  this  description,  the  value  and  correctness  of  the 
diagnosis  depend  upon  the  fact  that  all  other  causes  of  the  con- 
stitutional symptoms  (asthenia,  vomiting,  etc.),  except  Addison's 
disease,  can  be  excluded.  Now,  every  experienced  physician  knows 
that   diagnosis    by  exclusion    is    always   difficult    and   hazardous. 


24O  DISEASES   OE   THE    BLOOD   GLANDS. 

Hence  the  statement,  which  has  been  more  than  once  insisted 
upon,  that  for  the  purposes  of  a  positive  diagnosis  the  pigmentation 
is  the  most  valuable  symptom  of  Addison's  disease. 

As  a  positive  sign  of  Addison's  disease,  the  discoloration  of 
the  skin,  and  especially  the  pigmentation  of  the  mucous  mem- 
branes, may  be  ranked  with  the  rashes  of  the  eruptive  fevers. 
Many  different  conditions  may  produce  fever  ;  but  in  the  absence 
of  the  physical  signs  of  a  local  inflammation,  and  in  the  absence 
of  a  skin  eruption  and  the  symptoms  or  signs  of  a  characteristic 
local  lesion,  the  diagnosis  may  be  very  difficult  or  impossible. 
From  the  character  of  the  temperature  curve,  it  may  be  possible, 
even  in  the  absence  of  a  rash  or  local  lesion,  always  provided  that 
07ie  can  rely  upon  one's  poivers  of  excluding  a  local  inflammatory  lesion, 
to  suspect,  with  more  or  less  probability,  and  in  some  cases  even  to 
positively  diagnose,  a  particular  form  of  febrile  disease  ;  but  in 
most  cases  of  this  kind  the  diagnosis  must  necessarily  remain  more 
or  less  uncertain.  So  too  with  regard  to  Addison's  disease.  In 
the  absence  of  pigmentation,  one  may  suspect  that  the  asthenia 
and  other  constitutional  symptoms  which  are  present  are  due  to 
disease  of  the  suprarenal  capsules  ;  but  unless  one  can  be  very  sure 
of  one's  powers  of  exclusion,  it  may  be  impossible  to  definitely 
diagnose  that  condition.  The  presence,  however,  of  the  charac- 
teristic discoloration  of  the  skin  and  mucous  membranes  gives  a 
different  complexion  to  the  case,  and  enables  us  to  make  a  positive 
diagnosis.  Hence,  in  all  cases  of  suspected  Addison's  disease,  the 
presence  of  discoloration  of  the  skin,  and  more  particularly  of 
those  parts  of  the  skin  which  are  exposed  to  the  atmosphere,  which 
are  subjected  to  pressure  or  irritation,  and  in  which  pigment  deposits 
are  normally  most  abundant,  and  especially  the  presence  of  pig- 
mented patches  on  the  lips,  gums,  tongue,  and  the  under  surface  of 
the  tongue  and  buccal  mucous  membrane,  should  be  most  carefully 
looked  for.  I  attach  the  highest  diagnostic  value  to  the  presence 
of  pigmented  deposits  on  the  mucous  membranes. 

The  diagnosis  of  those  atypical  cases  in  which  there  are 
no  constitutional  symptoms. — In  not  a  few  cases  of  Addison's 
disease,  the  discoloration  of  the  skin  is,  as  we  have  seen,  the  first 
symptom  to  attract  attention,  and  in  some  rare  cases  it  seems  to 
be  well  marked  in  the  earlier  stages,  and  before  the  asthenia  and 
other  constitutional  symptoms  are  sufficiently  developed  to  be 
noticed. 

In  cases  of  this  kind,  a  positive  diagnosis  may  be  very  difficult, 
or  even  impossible.  One  may  suspect  that  the  pigmentation  is  due 
to  Addison's  disease  ;   but  in  the  absence  of  asthenia,  and  other 


ADDISON'S   DISEASE.  24 1 

constitutional  symptoms,  it  is  rarely,  if  ever,  possible  to  make  a 
positive  diagnosis. 

In  order  to  carry  the  diagnosis  farther  than  a  mere  supposition, 
all  other  possible  causes  of  skin  pigmentation  must  be  excluded. 
Even  in  those  cases  in  which  all  these  conditions  can  be  excluded, 
and  in  which  there  is  no  obvious  cause  for  the  discoloration  of  the 
skin,  it  is  impossible  to  do  more  than  suspect  Addison's  disease. 
When  constitutional  symptoms  are  entirely  absent,  it  is  rarely,  if 
ever,  justifiable  to  conclude  that  disease  of  the  suprarenal  capsules 
is  the  cause  of  the  pigmentation.  In  cases  of  this  kind,  we  may 
strongly  suspect  Addison's  disease,  but  we  must  be  content  to  wait 
for  the  development  of  constitutional  symptoms  before  committing 
ourselves  to  a  positive  diagnosis  of  that  condition. 

The  diagnosis  of  complicated  cases. — The  diagnosis  of  Addi- 
son's disease  in  complicated  cases  {i.e.,  in  cases  in  which  the 
pigmentation  and  other  symptoms  of  the  disease  are  superadded 
to  those  of  some  other  affection,  such  as  chronic  phthisis  or  spinal 
caries)  is  usually  a  matter  of  great  difficulty  and  uncertainty. 

The  difficulty  is  especially  great  in  cases  of  chronic  phthisis, 
and  is  due,  firstly,  to  the  fact  that  asthenia  and  constitutional 
symptoms  (which  more  or  less  closely  resemble  those  of  Addison's 
disease)  are  frequently  met  with  as  the  result  of  the  primary  disease 
(phthisis  or  spinal  caries),  and,  secondly,  that  in  some  cases  of  chronic 
phthisis,  marked  discoloration  of  the  skin,  and  in  rare  and  excep- 
tional cases,  of  the  tongue  and  buccal  mucous  membrane,  identical 
in  character  with  the  discoloration  of  Addison's  disease,  is  deve- 
loped. It  may,  however,  be  stated  that  in  chronic  phthisis  the  dis- 
coloration is  usually  limited  to  the  face  (forehead  and  skin  about 
the  nose  more  especially),  and  that  it  rarely  becomes  diffused  over 
the  whole  body,  as  in  Addison's  disease.  Further,  it  may  not  un- 
reasonably be  suggested  that  in  some  of  the  cases  of  phthisis  in 
which  the  skin  is  discoloured,  the  suprarenal  capsules  are  probably 
affected  (tubercular),  and  that  the  skin  pigmentation  is  in  reality  a 
symptom  of  Addison's  disease.  I  am  fully  aware  that  in  many  cases 
of  phthisis  with  skin  discoloration  the  suprarenal  capsules  have  been 
described  as  perfectly  healthy  after  death;  but  it  may,  I  think,  be 
doubted  whether  they  were  absolutely  normal  in  all  of  these  cases. 
Drs  Alezais  and  Arnaud  have  shown  that  in  a  considerable  propor- 
tion of  cases  of  phthisis  taken  at  random,  and  in  which  there  were  no 
symptoms  indicative  of  Addison's  disease  during  life,  the  suprarenal 
capsules  were  actually  tubercular  on  microscopical  examination. 
Now  if  this  is  so,  we  may  expect  a  fortiori  that  in  those  cases  of 
phthisis    in   which    symptoms   of  Addison's  disease   are   actually 

Q 


242  DISEASES   OF   THE   BLOOD   GLANDS. 

present,  the  suprarenal  capsules  will  be  tubercular  in  a  much 
larger  proportion  of  cases.  Further,  it  must  be  remembered  that, 
according  to  these  observers,  a  comparatively  slight  tubercular 
deposit  in  the  fibro-vascular  zone,  which  surrounds  the  suprarenal 
capsules,  and  especially  that  part  of  the  fibro-vascular  zone  which 
is  situated  on  the  posterior  surface  of  the  capsules,  may,  by  impli- 
cating the  pericapsular  nervous  ganglia  of  the  sympathetic,  lead  to 
the  production  of  skin  pigmentation  and  perhaps  of  the  other  symp- 
toms of  Addison's  disease.  Future  observers  will  not  have  to  be 
content  with  a  mere  naked-eye  examination  of  the  capsules  ;  in 
future,  before  concluding  that  the  skin  pigmentation  in  cases  of 
chronic  phthisis  is  due  to  the  phthisis  and  not  to  Addison's  disease, 
it  must  be  shown  by  microscopic  examination  that  the  suprarenal 
capsules  and  the  pericapsular  ganglia  are  sound.  Until  the  exact 
(microscopical)  condition  of  the  suprarenal  capsules  and  of  the  peri- 
capsular ganglia  has  been  determined  in  a  sufficient  number  of 
cases  of  phthisis,  with  skin  pigmentation,  it  is  altogether  premature 
to  conclude  that  the  skin  pigmentation  associated  with  phthisis  is 
due  to  the  phthisis  and  not  to  Addison's  disease. 

Fortunately,  in  cases  of  this  kind  the  diagnosis  is  a  matter  of 
scientific  interest  rather  than  of  practical  importance  ;  for  so  far  as 
prognosis  is  concerned,  the  result  is  very  much  the  same  in  both 
conditions.  Chronic  phthisis  with  pigmentation  of  the  skin  is,  like 
Addison's  disease,  a  condition  which  usually,  sooner  or  later, 
terminates  in  death. 

In  cases  of  this  kind  the  physician  has  to  ask  himself  whether 
the  local  lesion  in  the  lung  satisfactorily  and  sufficiently  accounts 
for  the  constitutional  symptoms.  In  cases  of  chronic  phthisis  it  is 
only  when  the  constitutional  symptoms  seem  greater  than  can 
reasonably  be  accounted  for  by  the  pulmonary  lesion  that  the  pig- 
mentation of  the  skin  can  with  any  degree  of  certainty  be  attributed 
during  life  to  a  lesion  of  the  suprarenal  capsules. 

The  differential  diagnosis  of  Addison's  disease,  and  of  other 
conditions  in  which  there  is  pigmentation  of  the  skin. — Before 
leaving  the  important  question  of  diagnosis,  it  may  perhaps  be  well 
to  mention  some  of  the  conditions  in  which  discoloration  of  the 
skin,  resembling  more  or  less  closely  the  discoloration  of  Addison's 
disease,  may  occur,  and  to  indicate  very  briefly  the  chief  points  of 
differential  diagnosis.  It  may,  however,  be  emphatically  stated 
that  a  careful  observer,  who  is  practically  acquainted  with  Addi- 
son's disease,  will  rarely  feel  any  great  difficulty  in  distinguishing 
these  conditions  from  Addison's  disease. 

The  following  are  some  of  the  conditions  which  (owing  to  the 


ADDISON'S   DISEASE.  243 

skin  discoloration  with  which  they  may  be  associated)  have  been 
mistaken  for  Addison's  disease  : — 

(1.)  Chronic  phthisis  with  skin  pigmentation. — The  differential 
diagnosis  has  already  been  considered. 

(2.)  Vagabond's  discoloration. — In  this  condition,  which  is  usually 
observed  in  old  and  extremely  dirty  vagrants  infested  with  lice,  the 
discoloration  is  not  uniform  ;  it  is  best  marked  on  the  exposed 
parts  of  the  body  (hands  and  face) ;  the  skin  is  rough,  harsh,  and 
inelastic,  and  often  marked  with  scratches  ;  the  buccal  mucous 
membrane  and  tongue  are  never  pigmented ;  the  patients  are 
generally  old  (whereas  Addison's  disease  is  very  rarely  indeed  met 
with  in  old  people).  The  constitutional  symptoms  suggestive  of 
Addison's  disease  are  absent ;  or,  if  asthenia  or  other  constitutional 
symptoms  suggestive  of  Addison's  disease  are  present,  they  are 
readily  accounted  for  by  the  presence  of  some  obvious  disease  or 
local  lesion.  The  history  of  the  case,  the  occupation  of  the  patient, 
and  the  fact  that  in  many  cases  the  discoloration  to  a  large  extent 
disappears  under  soap  and  water,  friction,  alkaline  baths,  good  feed- 
ing, rest  and  tonics,  afford  corroborative  evidence  of  the  true  nature 
of  the  condition. 

(3.)  Nitrate  of  silver  discoloration. — The  discoloration  is  only  or 
chiefly  marked  on  those  parts  which  are  exposed  to  light ;  the  tint 
is  quite  different  from  that  of  Addison's  disease  (more  leaden  and 
grey,  and  not  so  brown) ;  the  patient  has  either  recently  or  at 
some  former  period  been  treated  with  nitrate  of  silver  ;  and  the 
constitutional  symptoms  of  Addison's  disease  are  absent. 

(4.)  Arsenic  discoloration. — This  is  also  readily  distinguished 
from  Addison's  disease  by : — the  history  of  the  case  (the  fact  that 
the  patient  has  been  taking  arsenic  in  full  doses)  and  the  presence 
of  other  symptoms  indicative  of  chronic  arsenical  poisoning,  such  as 
dryness  of  the  throat,  itching  of  the  conjunctivae,  a  moist  condition 
of  the  palms  and  soles,  pains  in  the  abdomen,  chronic  diarrhoea, 
vomiting,  etc. 

In  (5)  chronic  scurvy,  (6)  pregnancy,  (7)  malarial  poisoning,  (8) 
syphilis,  (9)  malignant  disease,  (10)  exophthalmic  goitre,  and  (1 1)  osteoid 
arthritis,  the  skin  may  become  pigmented  and  discoloured.  The 
history  of  the  case,  the  associated  symptoms,  the  presence  or  absence 
of  definite  local  lesions,  the  progress  of  the  disease  and  the  effect  of 
treatment,  would  enable  an  experienced  observer  to  distinguish 
these  conditions  without  any  difficulty. 

(12.)  Diffuse  melanosis  with  pigmentation  of  the  skin. — In  these 
rare  cases  the  tint  of  the  discoloration  is  different — it  (always  ?) 
resembles  the  discoloration  produced  by  nitrate  of  silver  rather 


244  DISEASES   OF   THE   BLOOD   GLANDS. 

than  that  of  Addison's  disease ;  the  conjunctivae  may  be  dis- 
coloured as  well  as  the  skin  ;  free  pigment  granules  can  often 
be  detected  in  the  blood  ;  the  urine  becomes  black  on  exposure 
to  the  air,  and  (usually)  deposits  pigment  granules  ;  the  sputum 
may  contain  pigment  granules  ;  the  patient  is  emaciated  and 
usually  cachectic-looking  ;  the  starting-point  of  the  disease  may  be 
apparent  in  a  pigmented  mole  which  has  taken  on  malignant  action, 
or  in  a  tumour  of  the  eye-ball  ;  symptoms  and  signs  indicative  of 
secondary  deposits  in  the  internal  organs  (liver,  brain,  etc.)  are 
usually  (always  ?)  present,  and  the  superficial  lymphatic  glands  may 
be  enlarged,  and  are  in  some  (rare)  cases  obviously  melanotic. 

(13.)  Leucoderma. — The  sharply-defined  character  of  the  pig- 
mented areas  (the  circular  form  of  the  white  patches  and 
their  clean-cut  edges)  at  once  distinguish  simple  uncomplicated 
leucoderma  from  Addison's  disease.  It  must,  however,  be  remem- 
bered that  leucoderma  is  sometimes  associated  with  Addison's 
disease.  In  the  sixth  case  described  by  Addison,  leucoderma  was 
(probably)  present,  and  in  another  case,  which  is  beautifully  repre- 
sented in  his  memoir  by  a  coloured  drawing,  but  in  which  there 
was  no  post  mortem,  he  states  : — "  I  entertain  no  doubt  whatever 
that  the  capsules  were  diseased."  A  case  of  the  same  kind  (sup- 
posed Addison's  disease  with  leucoderma,  not,  however,  verified,  by 
post-mortem  examination)  came  under  my  own  notice  several  years 
ago  (Case  V.).  Amongst  the  recorded  cases  of  Addison's  disease 
the  presence  of  leucoderma  is  several  times  mentioned. 

(14.)  Pigmentation  of  the  skin,  associated  with  chronic  peritonitis, 
malignant  disease  in  tJie  abdomen,  pelvis,  etc. — In  cases  of  this  kind 
the  differential  diagnosis  is  often  most  difficult,  and  sometimes,  I 
believe,  impossible.  Nor  is  this  to  be  wondered  at  when  it  is 
remembered  that  pigmentation  of  the  skin  exactly  similar  to  that 
of  Addison's  disease  has  in  some  cases  resulted  from  malignant 
disease  involving  the  abdominal  sympathetic,  and  that  in  malignant 
diseases  of  the  abdomen  all  the  other  constitutional  symptoms  of 
Addison's  disease  may  be  present. 

The  mode  of  onset  of  the  disease,  the  rapidity  of  its  course,  the 
age  of  the  patient,  especially  the  presence  of  marked  emaciation, 
and  the  fact  that  there  is  evidence  (in  the  form  of  symptoms  and 
signs)  of  localised  organic  disease  in  the  abdomen  or  pelvis,  are  the 
points  of  most  importance  in  distinguishing  such  cases  from  cases 
of  Addison's  disease. 

(15.)  Localised  pigmentation  due  to  exposure  to  the  sun,  and 
especially  to  the  sun  and  sea-air,  and  discolorations  of  the  skin  due  to 
pityriasis  versicolor,  and  other  forms  of  skin  disease  have  in  some 


ADDISON'S   DISEASE.  245 

cases  been  mistaken  for  the  discoloration  due  to  Addison's  disease. 
The  diagnosis  in  such  cases  is  so  obvious  that  the  points  of  dis- 
tinction need  not  be  enumerated  in  detail. 

( 1 6.)  Chronic  pigmentation  of  the  skin  resembling  that  of  A  ddison's 
disease,  but  without  any  constitutional  symptoms,  and  not  due  to  any 
obvious  cause. — Two  cases  of  this  kind  are  described  in  the  "  Trans- 
actions of  the  Clinical  Society  of  London,"  for  the  year  1881,  the 
first  by  Dr  Crocker,  and  the  second  by  Dr  Carrington.  (See  pages 
152  and  157.)  In  Dr  Crocker's  case,  the  discoloration  had  lasted 
for  eight  years.  I  simply  mention  these  cases  because  of  their 
rarity  and  obscurity,  and  in  the  hope  that  some  future  observer  may 
be  able  to  explain  their  true  nature,  and  to  decide  whether  they  are 
in  any  way  related  to  Addison's  disease.  Fortunately  for  diagnosis, 
cases  of  this  kind  are  exceedingly  rare.  It  is  obvious  that  if,  in 
either  of  these  cases,  the  patient  had  been  temporarily  debilitated 
from  any  cause,  or  had  been  suffering  from  gastro-intestinal  irrita- 
tion or  from  pain  in  the  abdomen  or  back,  the  distinction  from 
Addison's  disease  might  (for  the  time  at  least)  have  been  im- 
possible. 

(17.)  Pernicious  ancemia. — In  some  cases  of  pernicious  anaemia, 
in  which  no  arsenic  has  been  administered,  the  skin  becomes  pig- 
mented and  the  clinical  picture  closely  resembles  that  of  Addison's 
disease.  Several  cases  of  this  kind  have  come  under  my  own  notice 
(see  Cases  XXVII.,  XXXI.,  XL.,  and  XLIV.) ;  in  two  of  these 
cases  (XL.  and  XLIV.)  the  suprarenal  capsules  were  found,  on 
post-mortem  examination,  to  be  normal ;  in  the  other  two  cases, 
there  was  no  autopsy.  The  similarity  of  the  constitutional  symp- 
toms (profound  and  causeless  asthenia,  little  or  no  loss  of  fat, 
debility  of  the  heart's  action,  attacks  of  causeless  vomiting  and 
diarrhoea),  the  absence  of  any  local  visceral  disease  to  account  for 
the  symptoms,  the  fact  that  in  both  diseases  the  colour-index  may 
be  above  the  normal,  and  the  fact  that  the  pigmentation  of  the 
skin  may  be  identically  the  same  in  the  two  diseases,  are  points  of 
close  resemblance.  But  the  condition  of  the  blood  is  distinctive. 
In  pernicious  anaemia,  the  bloodlessness  is  profound  ;  whereas,  in 
Addison's  disease,  there  is  either  no  anaemia  or  the  degree  of  anaemia 
is  slight.  In  most  cases  of  Addison's  disease,  the  lips  are  well, 
indeed  in  some  cases  too  highly,  coloured.  By  an  accurate  estima- 
tion of  the  red  corpuscles,  and  by  observing  the  microscopical 
characters  of  the  red  corpuscles,  it  is,  so  far  as  my  observation 
enables  me  to  judge,  always  possible  to  determine  with  certainty 
whether  the  case  is  one  of  uncomplicated  pernicious  anaemia,  on  the 
one  hand,  or  of  uncomplicated  Addison's  disease  on  the  other.    But 


246  DISEASES   OF   THE   BLOOD   GLANDS. 

whether  it  is  possible  to  definitely  exclude  Addison's  disease  in 
those  cases  of  pernicious  anaemia  in  which  the  skin  is  deeply 
pigmented,  and  in  which  the  pigmentation  is  not  the  result  of 
arsenic,  is  another  question.  It  is  possible  that  the  two  conditions 
may  occur  in  combination,  but,  so  far  as  I  know,  no  case  has  hitherto 
been  recorded  in  which  it  has  been  proved  by  post-mortem  observa- 
tion that  this  actually  was  the  case.  In  two  of  my  cases  of  per- 
nicious anaemia  in  which  Addison's  disease  was  suspected  during 
life,  the  suprarenals  were  healthy  after  death.  I  have  not  seen  any 
case  of  pernicious  anaemia  in  which  the  pigmentation  of  the  mucous 
membranes  characteristic  of  Addison's  disease  was  present.  If  any 
case  of  pernicious  anaemia  should  come  under  my  notice  in  which 
the  mucous  membranes  were  pigmented  as  in  Addison's  disease,  I 
should  feel  justified  in  diagnosing  a  combination  of  the  two  con- 
ditions. 

(18.)  Diabetic  bronzing. — In  some  cases  of  hypertrophic  cirrhosis 
of  the  liver  associated  with  the  presence  of  sugar  in  the  urine,  the 
skin  becomes  so  markedly  pigmented  that  the  term  diabete  bronze 
has  been  given  to  the  condition  by  Hanot  and  Chauffard.*  The 
condition  is  at  once  distinguished  from  Addison's  disease  by  the 
clinical  features  (enlargement  of  the  liver,  pigmentation  of  the  skin, 
and  the  presence  of  sugar  in  the  urine — diabetes). 

Morbid  Anatomy. 

Typical  lesion. — In  the  great  majority  of  cases  of  Addison's 
disease,  both  suprarenal  capsules  are  more  or  less  completely 
destroyed  by  a  fibro-caseous  degeneration,  as  it  has  been  termed. 
Most  authorities  are  now  agreed  that  this  lesion  is  tubercular  in 
character,  although  in  several  cases  which  have  been  carefully 
examined  no  tubercle  bacilli  have  been  found  ;  and  in  one  instance 
in  which  Delepine  injected  the  caseous  material  into  a  guinea-pig, 
no  tubercles  were  developed. 

In  the  great  majority  of  cases,  the  capsules  are  enlarged  ;  but 
in  some  they  are  of  normal  size,  and,  in  a  few  cases,  they  are 
smaller  than  normal. 

In  typical  cases  the  capsules  are  enlarged,  firm,  nodulated, 
irregular  in  shape,  and  adherent  to  the  surrounding  structures. 

The  appearances  which  the  diseased  capsules  present  on  section 
vary  with  the  stage  of  the  disease  and  the  nature  of  the  secondary 
(degenerative)  changes  which  have  taken  place.     In  most  cases,  the 

*  "  Revue  de  Medecine,"  1882,  p.  386. 


ADDISON'S   DISEASE.  247 

distinction  between  the  cortical  and  medullary  parts  of  the  organ  is 
no  longer  recognisable.  In  fresh  specimens,  the  cut  surface  usually 
has  a  mottled  or  marbled  appearance,  due  to  "  the  admixture  of 
two  materials  of  different  colour  and  consistence. 

"  One  of  these  materials  is  a  translucent  tissue  of  firm  consistence 
and  of  a  grey  or  greenish-grey  colour,  at  least  when  freshly  cut,  but 
which  rapidly  assumes  a  reddish  hue  on  exposure  to  air. 

"  The  other  material  is  of  an  opaque  yellow  or  cream  colour,  and 
generally  assumes  the  form  of  irregular,  roundish  masses  of  a  more 
or  less  friable  consistence  embedded  in  the  translucent  tissue  from 
which  they  can  in  many  cases  be  easily  enucleated."  *  The  yellow 
opaque  masses  are  caseous  foci.  In  some  cases,  gritty  calcareous 
nodules  are  present  in  the  midst  of  the  caseous  material.  In  long- 
standing cases,  the  whole  capsule  may  be  converted  into  a  cheesy, 
putty-like,  or  calcareous  mass.  In  other  cases,  the  caseous  por- 
tions, instead  of  becoming  dry,  cheesy,  or  calcareous,  soften  and 
liquefy  ;  numerous  small  cavities  containing  a  thick  creamy  fluid 
may  then  be  formed  in  the  interior  of  the  diseased  organ,  or  the 
whole  capsule  may  be  converted  into  a  cyst  containing  a  thick 
yellow  fluid  which  looks  like  pus.  The  fibrous,  caseous,  or  calcareous 
changes  appear  to  be  simply  the  ultimate  result  of  a  tubercular 
lesion. 

The  relative  proportions  of  the  translucent,  exudation-like,  and 
of  the  fibrous,  caseous,  or  calcareous  materials,  vary  greatly  in 
different  cases,  and  depend,  in  great  part  at  least,  upon  the  length 
of  time  which  the  lesion  has  existed. 

In  the  early  stages  of  the  disease,  the  translucent  exudation-like 
material  predominates,  and  the  capsules  may  then  be  very  much 
enlarged.  In  the  later  stages,  when  the  fibrous,  caseous,  and 
calcareous  changes  are  far  advanced,  the  capsules  may  be  smaller 
than  normal. 

In  the  great  majority  of  cases  of  Addison's  disease,  both  cap- 
sules are  affected  and  usually  completely  destroyed  by  the  fibro- 
caseous  (tubercular)  lesion  ;  but  in  some  cases  the  lesion  of  the 
capsules  is  more  advanced  on  one  side  than  on  the  other.  In  a  few 
of  the  recorded  cases  the  lesion  of  the  capsules  has  been  limited  Jo 
localised  areas ;  and  in  rare  cases  one  capsule  only  has  been  involved. 

Simple  fibrous  atrophy  and  fatty  transformation  of  the 
suprarenal  capsules. — In  most  of  the  cases  in  which  the  capsules 
are  smaller  than  normal  and  replaced  by  fibrous  tissue,  the  fibroid 
change  seems  to  be  merely  a  late  (secondary)  result  of  the  typical 

*  "Addison's  Disease,"  by  Dr  Greenhow,  p.  24. 


248  DISEASES   OF   THE   BLOOD   GLANDS. 

fibro-caseous  (tubercular)  lesion  which  I  have  just  described.  But 
cases  are  occasionally  though  rarely  met  with  in  which  the 
atrophy  does  not  seem  to  be  satisfactorily  accounted  for  in  this 
way.  A  considerable  number  of  cases  of  Addison's  disease  have 
been  recorded — and  Case  III.  is  an  illustration — in  which  the  cap- 
sules were  represented  by  a  mere  shell  of  fibrous  tissue  (simple 
atrophy) ;  or  in  which  the  capsular  (secreting)  tissue  seemed  to  be 
replaced  by  fibrous  tissue  (cirrhotic  atrophy). 

In  some  cases  of  this  kind,  there  were  no  indications  of  any 
preceding  inflammatory  lesion,  and  so  far  as  I  can  see,  no  reason 
whatever  to  suppose  that  the  atrophy  or  fatty  change  was  the 
result  of  the  fibro-caseous  (tubercular)  lesion  described  above. 

In  other  and  still  rarer  cases,  the  suprarenal  capsules  appear  to 
have  been  completely  absent,  or  replaced  by  fat.  I  have  recorded 
a  remarkable  case  in  point  (see  Case  IV.). 

Dr  Sydney  Coupland  has  thrown  out  the  suggestion  that  in 
these  cases  the  atrophy  of  the  capsules  is  a  secondary  (and  presum- 
ably, if  I  understand  him  aright,  trophic)  result  of  a  primary  lesion 
■of  the  abdominal  sympathetic  ;  but,  so  far  as  I  know,  there  are  no 
facts  in  favour  of  this  hypothesis.  There  can,  I  think,  be  little 
doubt  that  in  typical  cases  of  Addison's  disease,  the  lesion  of  the 
capsules  is  primary,  and  the  lesions  in  the  sympathetic  secondary 
thereto  ;  and,  so  far  as  I  see,  there  is  no  reason  to  suppose  that  this 
pathological  sequence  is  reversed  in  the  rare  cases  to  which  I  am 
at  present  more  particularly  referring. 

The  condition  of  the  suprarenal  nerves  and  the  abdominal 
sympathetic. — As  I  have  already  stated,  in  typical  cases  of  Addi- 
son's disease  the  enlarged  and  indurated  capsules  are  usually  more 
or  less  firmly  adherent  (clearly  as  the  result  of  inflammatory 
changes)  to  the  surrounding  parts  (kidneys,  vena  cava,  aorta, 
pancreas,  stomach,  etc.). 

The  nerves  which  pass  in  such  abundance  between  the  capsules 
and  the  semilunar  ganglia,  and  the  semilunar  ganglia  themselves, 
are  in  a  considerable  proportion  of  cases  implicated  in  these  in- 
flammatory changes.  On  naked-eye  examination,  they  may  be 
seen  to  be  enlarged,  thickened,  indurated,  and  sometimes  injected 
and  redder  than  normal.  On  microscopic  examination,  appearances 
clearly  indicative  of  inflammatory  induration  (increase  of  connec- 
tive tissue,  infiltration  with  leucocytes,  enlargement  and  engorge- 
ment of  the  blood-vessels)  may  be  present  in  the  fibrous  covering 
of  the  nerves  ;  and,  in  some  cases,  the  proper  nervous  elements 
fnerve  tubes  and  ganglion  cells)  arc  also  inflamed,  degenerated, 
or  atrophied. 


ADDISON'S   DISEASE.  249 

These  inflammatory  changes  in  the  nerve  tubes  and  semilunar 
ganglia  are  probably  secondary — the  result  of  irritation  and  in- 
flammation excited  by  the  (primary)  fibro-caseous  (tubercular) 
lesion  of  the  capsules. 

Further,  it  is  important  to  note — for  this  point  has  a  very 
distinct  bearing  upon  the  pathological  physiology  of  the  disease — 
that  in  a  considerable  number  of  cases  in  which  the  suprarenal 
capsules  have  been  completely  destroyed  by  the  typical  fibro- 
caseous  (tubercular)  lesion,  no  pathological  alterations  have  been 
found,  even  on  careful  microscopical  examination,  in  the  semilunar 
ganglia  and  the  large  nerve  trunks  forming  the  solar  plexus  ;  and 
that  in  other  cases  in  which  the  suprarenal  capsules  are  completely 
atrophied,  absent,  or  replaced  by  fat,  the  suprarenal  nerves  and 
the  solar  plexuses  have  appeared  to  be  quite  normal.  Neverthe- 
less, it  may,  I  think,  be  confidently  stated  that  in  most  cases  of 
Addison's  disease  in  which  the  lesion  is  typical  the  nerve  tubes 
which  are  directly  connected  with  the  diseased  capsules  are  in- 
volved and  inflamed. 

The  condition  of  the  suprarenal  nerves  in  Addison's  disease 
has  been  very  minutely  studied  by  two  French  observers,  Drs 
Alezais  and  Arnaud.  They  have  shown  that  true  sympathetic 
nervous  ganglia,  which  they  have  termed  pericapsular  nervous 
ganglia,  are  situated  on  the  surface  of,  and  sometimes  actually  in 
the  substance  of,  the  fibrous  capsule  which  envelops  the  supra- 
renal bodies. 

They  claim  to  have  demonstrated,  firstly,  that  in  several  cases 
of  Addison's  disease,  in  which  the  pigmentation  and  other  charac- 
teristic symptoms  were  present,  these  pericapsular  nervous  ganglia 
were  invaded  by  the  tubercular  process  which  originated  in  the 
capsule  ;  and,  secondly,  that  in  some  cases  in  which  the  character- 
istic fibro-caseous  (tubercular)  lesion  of  the  capsules  was  present, 
but  in  which  there  was  no  pigmentation,  the  pericapsular  nervous 
ganglia  were  not  implicated. 

They,  therefore,  conclude  that  the  essential  cause  of  the  pig- 
mentation and  other  characteristic  symptoms  of  Addison's  disease 
is  implication  of  these  pericapsular  nervous  ganglia  by  a  tubercular 
process  which  extends  from  the  suprarenal  capsules. 

In  the  article  on  Addison's  disease  in  my  Atlas  of  Clinical 
Medicine  I  have  quoted  these  observations  in  full  (vol.  i.,  pp.  64, 
65,  and  66). 

Cancerous  destruction  of  the  capsules. — Most  authorities 
deny  that  the  symptoms  of  Addison's  disease  are  produced  by 
cancerous  destruction  of  the  suprarenal  capsules.     Sir  Samuel  Wilks, 


250  DISEASES   OF   THE    BLOOD   GLANDS. 

for  example,  says  : — "  There  is  very  strong  evidence  in  favour  of 
the  opinion  that  the  change  in  the  capsules  is  peculiar,  uniform 
in  character,  and  primary  in  its  nature.  We  mean  by  this  that 
it  does  not  consist  of  various  forms  of  disease,  and  is  not  a 
mere  accidental  part  of  a  malady  affecting  the  body  generally,  but 
that  it  is  as  much  a  primary  and  essential  disease  as  cirrhosis  of 
the  liver  or  a  granular  degeneration  of  the  kidney.  It  is  unfortu- 
nately true  that  Addison,  not  content  with  placing  on  record  his 
few  genuine  examples  of  the  complaint,  hazarded  a  conjecture 
that  cancer  or  any  other  destructive  agency  might  develop  the 
symptoms,  but  he  gave  no  instances  in  corroboration  of  it,  and  no 
single  writer  has  published  a  single  case  where  cancer,  tubercle,  or, 
indeed  any  form  of  benignant  or  malignant  growth  has  been  pro- 
ductive of  the  genuine  symptoms,  nor,  indeed,  has  any  case  been 
recorded  where  degenerative  changes  other  than  those  previously 
described  have  given  rise  to  the  complaint.  In  all  cases,  where 
the  symptoms  have  been  well  marked,  the  change  in  the  capsules 
has  been  of  one  kind,  and  essentially  primary."  And  again,  "We 
might  mention  that  in  several  articles  to  be  found  both  in  French 
and  German  works  on  the  subject  of  Addison's  disease,  the  authors 
have  collected  some  hundreds  of  cases  where  the  suprarenal  organs 
were  diseased,  also  cases  where  the  skin  was  discoloured,  and 
where  asthenic  symptoms  prevailed.  On  carefully  perusing  these,, 
the  position  we  have  taken  up  is  clearly  proved,  viz.,  that  the 
symptoms  which  Addison  described  can  be  associated  with  only- 
one  form  of  disease  of  the  capsules,  although  this  is  not  the  conclu- 
sion of  the  authors  themselves,  who  have  also  mistaken  cases  of 
leucoderma  and  other  cutaneous  affections  for  it."  * 

With  this  opinion  I  cannot  altogether  agree.  That  malignant 
disease  (cancer  and  sarcoma)  of  the  suprarenal  capsules  very  rarely 
indeed  results  in  the  production  of  all  of  the  symptoms  character- 
istic of  Addison's  disease  I  fully  admit ;  but  I  do  not  feel  in  a 
position  to  say  dogmatically  that  it  cannot  produce  them. 

And  in  this  connection  I  would  especially  emphasise  the  fact 
that  in  the  majority  of  cases  of  cancerous  destruction  of  the  cap- 
sules, the  symptoms  of  Addison's  disease  have  been  said  to  be 
absent  because  pigmentatio)i  of  the  skin  and  mucous  membranes  was 
not  present.  But  it  must  be  remembered  that  in  typical  (tubercular) 
destruction  of  the  capsules,  pigmentation  may  be  very  slight,  or 
indeed  altogether  absent ;  and  that  this  is  particularly  apt  to  occur 
in  those  cases  (as  in  cancer)  in  which  the  lesion  runs  a  rapid  course, 

*  Russell  Reynolds'  "  System  of  Medicine,"  Vol.  v.,  pp.  361,  362. 


ADDISON'S   DISEASE.  25  I 

in  other  words  in  which  the  destruction  of  the  suprarenal  capsules 
is  more  quickly  produced  than  in  the  average  run  of  (typical)  cases. 

The  argument,  then,  that  because  pigmentation  is  absent  the 
symptoms  of  Addison's  disease  are  absent,  is  a  fallacious  one.  One 
might  as  well  say  that  in  the  typical  (tubercular)  cases  in  which 
pigmentation  is  absent  the  disease  is  not  Addison's  disease. 

Further,  every  one  now  admits  that  simple  (non-tubercular) 
atrophy  of  the  capsules  may  produce  all  the  characteristic  sym- 
ptoms of  Addison's  disease  ;  and,  as  Case  IV.  shows,  fatty  trans- 
formation of  the  capsules  may  produce  all  the  characteristic 
symptoms  of  Addison's  disease. 

I  see  no  a  priori  reason,  therefore,  why  malignant  disease 
(cancer,  sarcoma)  of  the  capsules  may  not  produce  the  characteristic 
symptoms  of  Addison's  disease ;  and,  as  a  matter  of  fact,  a  case 
reported  by  Dr  Gage  of  Boston  seems  to  me  to  support  this  view. 
Dr  Greenhovv,  it  is  true,  while  fully  admitting  that  the  symptoms 
were  characteristic  of  Addison's  disease,  says  :  "  In  this  case  there 
appears  to  have  been  no  microscopical  examination  of  the  diseased 
organs,  and  although  the  description  is  less  clear  than  in  the  two 
previous  cases,  it  presents  on  the  whole  a  greater  resemblance  to 
the  lesion  in  Addison's  disease  than  to  cancer."  But  with  his 
opinion  as  to  the  nature  of  the  lesion  I  cannot  agree.  The  lesion 
of  the  capsules  was,  in  my  opinion,  more  like  cancer  than  the  fibro- 
caseous  (tubercular)  lesion  characteristic  of  Addison's  disease. 
Further,  the  patient's  breast  had  been  removed  two  years  pre- 
viously for  cancer  ;  and  on  post-mortem  examination  a  secondary 
deposit,  such  as  might  quite  well  occur  in  cancer,  but  which,  so  far 
as  I  know,  has  never  been  observed  in  connection  with  the  ordinary 
(fibro-caseous)  lesion  of  Addison's  disease,  was  found  in  the  liver. 
In  addition,  the  medical  men  who  made  the  post  mortem,  and  who 
saw  the  morbid  condition  in  its  recent  state,  report,  without  any 
apparent  doubt,  that  it  was  a  case  of  cancer.  The  following  is  the 
report  of  the  pathological  appearances  : — 

"Autopsy. — Not  much  emaciation;  flesh  soft  and  flabby.  Discoloration 
somewhat  faded,  but  well  marked.  One  inch  of  fat  overlies  sternum  and 
abdomen  ;  much  fat  inside  abdomen.  On  removal  of  stomach  and  intestines 
two  large,  almost  spherical,  tumours  are  observed,  occupying  the  place  of  the 
suprarenal  capsules,  joined  together  across  the  vertebrae  by  a  thickened,  cor- 
rugated mass  of  enlarged  and  diseased  lymphatic  glands.  Tumour  on  the  right 
side  somewhat  larger  than  that  on  the  left,  being  two  and  a  half  inches  in 
diameter,  and  adhering  by  a  strong  and  broad  attachment  to  the  under  surface 
of  the  liver.  From  this  point  of  attachment  several  broad  lines  of  reddish-white 
soft  deposit  radiate  into  the  substance  of  the  liver  for  one  and  a  half  inches, 
resembling  soft  cancer,  as  sometimes  seen  infiltrated  in  that  organ. 


252  DISEASES   OF   THE   BLOOD   GLANDS. 

"  The  tumours,  externally,  present  a  soft  uniform  glistening  surface.  (No 
italics  in  the  original.) 

"  On  section,  a  dense,  firm,  fibrous  texture,  making  a  smooth  surface,  at  first 
white,  but  soon  covered  by  a  bright  orange-yellow  exudation,  which,  after 
exposure  to  the  air,  became  a  dingy,  greenish-brown.  The  diseased  lymphatic 
gland  was  of  a  very  similar  texture,  but  gave,  on  section,  none  of  the  yellow 
fluid.  (No  italics  in  the  original.)  Nothing  else  abnormal  in  thorax  or 
abdomen.  Head  not  examined."  (Gage,  "Boston  Medical  and  Surgical 
Journ.,"  vol.  lxxi.,  p.  69  ;  quoted  by  Greenhow,  p.  190.) 

In  a  recent  paper,  Drs  Rolleston  and  Marks  make  the  following 
statement  with  regard  to  the  presence  of  symptoms  of  Addison's 
disease  in  cases  of  primary  malignant  disease  of  the  suprarenal 
capsules  : — "  The  consensus  of  experience  and  opinion  is  decidedly 
against  the  view  that  secondary  malignant  growths  in  these  bodies 
induce  symptoms  of  Addison's  disease,  and  probably  this  may  be 
explained  by  supposing  that  the  primary  malignant  disease  kills 
the  patient  before  there  is  time  for  the  characteristic  symptoms  of 
Addison's  disease  to  appear.  Much  the  same  appears  to  be  the  case 
with  regard  to  primary  growths  in  the  suprarenal  bodies.  It  does  not 
appear  that  the  complete  clinical  picture  of  Addison's  disease  has 
been  presented  by  any  one  case  of  primary  malignant  disease  of 
suprarenal  bodies,  even  when  both  organs  have  been  invaded  ;  but 
some  of  the  symptoms  of  Addison's  disease  may  occur  in  primary 
adrenal  new  growths.  Pigmentation  has  been  observed  very  rarely. 
Vomiting,  probably  due  to  irritation  of  the  abdominal  sympathetic, 
was  a  marked  symptom  in  some  cases.  Asthenia  was  very  notable 
in  some  cases,  but  is  perhaps  generally  not  more  marked  than  in 
patients  dying  of  malignant  disease  elsewhere.  Pain  in  the  back, 
often  seen  in  Addison's  disease,  may  also  occur  in  malignant 
disease,  and  suggest  an  aneurism  or  deep-seated  new  growth."  They 
sum  up  their  conclusions  in  the  following  remarks  : — "  The  clinical 
picture  of  Addison's  disease  is  not  presented,  but  in  some  rare 
instances  it  is  partially,  though  imperfectly,  suggested  in  cases  of 
primary  malignant  disease  of  the  suprarenal  capsules."  * 

On  theoretical  grounds,  and  granting,  as  I  think,  that  the 
symptoms  of  Addison's  disease  are  partly  due  to  destruction  of  the 
capsules,  and  partly  to  secondary  disturbances,  probably  irritative 
in  character,  which  are  produced  in  the  nerves  which  surround  and 
are  in  connection  with  the  suprarenal  bodies,  I  see  no  reason  why 
any  lesion  of  the  capsules,  provided  only  that  it  is  sufficiently 
destructive,  sufficiently  chronic  and  (perhaps)  sufficiently  irritative 

*  "American  Journal  of  the  Medical  Sciences,"  October  1898,  p.  396. 


ADDISON'S   DISEASE.  253 

in  character,  may  not  produce  the  symptoms  of  Addison's 
disease.* 

The  absence  of  the  characteristic  symptoms  in  cases  of  malignant 
destruction  of  the  capsules  may  probably  be  due  to  a  variety  of 
circumstances,  viz.  : — 

(a.)  That  the  cancerous  destruction  is  incomplete  : 

(b.)  That  accessory  suprarenal  bodies,  which  were  not  involved 
in  the  cancerous  lesion,  were  present  : 

(V.)  That  the  cancerous  destruction  usually  runs  too  rapid  a 
course  to  allow  of  the  production  of  the  symptoms  of  Addison's 
disease  :  or, 

{d.)  That  the  cancerous  lesion  is  not  sufficiently  irritating  to 
the  nerves.  For  some  years  past  I  have  suggested  in  my  lectures 
that  the  tubercle  bacillus  perhaps  secretes  some  chemical  substance 
which  exerts  a  special  and  peculiarly  irritative  effect  upon  the 
nerves. 

Drs  Alezais  and  Arnaud,  who  think  that  the  symptoms  of 
Addison's  disease  are  due  to  involvement  of  the  pericapsular 
sympathetic  ganglia,  explain  the  absence  of  symptoms  of  Addison's 
disease,  in  cases  of  cancerous  destruction  of  the  capsules,  by  the 
fact  that  new  growths  which  originate  in  the  suprarenal  capsules 
usually  grow  from  within  outwards,  and  that  they  are  limited  by 
the  fibrous  covering  of  the  gland,  which,  in  many  cases,  becomes 
thickened  and,  as  it  were,  bars  further  progress  of  the  new  growth, 
and  prevents  the  invasion  and  implication  of  the  pericapsular 
nervous  ganglia  and  other  adjacent  structures. 

Suprarenal  capsules  healthy ;  disease  of  abdominal  sym- 
pathetic.— In  some  rare  and  quite  exceptional  cases,  in  which 
bronzing  of  the  skin  and  the  other  symptoms  of  Addison's  disease 
were  present  during  life,  the  suprarenal  capsules  were  found,  on 
post-mortem  examination,  to  be  healthy,  but  the  abdominal  sym- 
pathetic (solar  plexus  and  semilunar  ganglia)  was  involved  in  a 
mass  of  new  growth.  Thus,  in  a  case  of  Hodgkin's  disease,  reported 
by  Sir  William  Gowers,  "  the  glandular  enlargement  was  general, 
but  in  the  thoracic  and  abdominal  cavities  it  was  very  great.  The 
suprarenal  body  on  each  side  was  healthy,  but  the  nerves  from 
each   passed  into   the   mass  of  gland   growth  by  which  the  solar 

*  This  part  of  the  article  was  written  before  I  had  read  the  important  article 
of  Drs  Alezais  and  Arnaud  ;  but  I  see  no  reason  to  modify  it,  though  it  must  be 
noted  that  if  the  views  of  these  observers  are  correct,  the  disease  is  due  not 
to  irritation  but  to  destruction  of  the  nervous  structures  in  the  immediate  neigh- 
bourhood of  the  capsules — destruction  of  the  pericapsular  nervous  ganglia  of 
the  sympathetic. 


254  DISEASES   OF   THE    BLOOD   GLANDS. 

plexus  was  involved.  The  bronzing  of  the  skin  was  striking,  and 
had  the  distribution  characteristic  of  Addison's  disease."*  In 
another  case  of  Hodgkin's  disease  recorded  by  Professor  Paget,  in 
which  very  marked  pigmentation  resembling  in  all  respects  that 
met  with  in  Addison's  disease  was  present  during  life,  the  supra- 
renal capsules  appeared  normal  in  every  respect,  but  the  splanchnic 
nerves,  semilunar  ganglia,  and  solar  plexus,  were  enveloped  in  a 
mass  of  enlarged  retro-peritoneal  glands  lying  in  front  of  the  spine. 
The  semilunar  ganglia  could  not  be  found.! 

Unilateral  disease  of  the  suprarenal  capsules. — In  the  great 
majority  of  cases  of  Addison's  disease,  both  capsules  are  affected 
and  usually  completely  destroyed  by  the  fibro-caseous  (tubercular) 
lesion.  In  many  cases,  however,  the  lesion  of  the  capsules  is  much 
more  advanced  on  one  side  than  on  the  other  ;  in  a  few  cases  the 
lesion  of  the  capsules  is  localised  and  limited  to  the  surface  of  the 
capsules  and  the  adjacent  pericapsular  tissues  ;  and  in  rare  cases 
one  capsule  only  is  involved. 

Some  writers  deny  that  the  lesion  of  the  capsules  is  ever  limited 
to  one  capsule  ;  but  in  this  they  are,  I  think,  mistaken.  I  have 
myself  recorded  a  case  (Case  XII.),  which  was,  I  believe,  a  case 
of  Addison's  disease,  in  which  one  capsule  only  (so  far  as  the  naked- 
eye  examination  enabled  me  to  judge)  was  affected.  Dr  Greenhow, 
in  his  work  on  Addison's  disease,  details  more  than  one  case  of  the 
same  kind  (see  p.  67).  In  one  of  the  cases  recently  reported  by 
Drs  Alezais  and  Arnaud,}  the  right  capsule  only  was  affected. 
This  case,  which  was  complicated  with  phthisis,  is  of  special  value 
and  importance,  for  the  pigmentation  affected  the  buccal  mucous 
membrane  as  well  as  the  skin,  and  the  suprarenal  capsules  were 
carefully  examined  with  the  microscope. 

If  the  view  of  the  pathology  of  the  disease  which  I  think  the 
most  probable  is  correct,  viz.,  that  some  of  the  symptoms  of 
Addison's  disease  are  due  to  destruction  of  the  capsules,  while 
others  are  due  to  implication  of  the  nervous  structures  with  which 
they  are  connected,  it  is  reasonable  to  suppose  that  the  characteristic 
symptoms  may  be  developed  in  some  cases  in  which  one  capsule 
only  is  diseased.  The  fact  that  in  many  cases  of  Addison's  disease 
the  lesion  is  much  more  advanced  in  one  capsule  than  in  the  other 
is  in  favour  of  this  view  ;  for  it  is  probable  that  if,  in  some  cases  of 
this  kind   (i.e.,  cases  in   which  the  capsular  lesion  is   much   more 

*  Russell  Reynolds'  "System  of  Medicine,"  Vol.  v.,  p.  316. 

t  "  Lancet,''  1879,  Vol.  i.,  p.  25S. 

%  "Revue  de  Medecine,"  10th  April  1891.     Obs.  III.,  p.  298. 


ADDISON'S   DISEASE.  255 

advanced  on  one  side  than  the  other),  the  patient  had  died,  and  the 
capsules  had  been  examined  at  an  early  stage  of  the  disease,  it 
would  have  been  found  that  one  capsule  only  was  affected. 

Pathological  alterations  in  other  organs. — In  addition  to  the 
lesions  of  the  capsules  and  of  the  abdominal  sympathetic  which 
have  just  been  described,  other  pathological  changes  are  not  infre- 
quently met  with  in  Addison's  disease. 

The  abdominal  glands  are,  in  many  cases,  enlarged,  and  in  some 
caseous  ;  old  or  recent  tubercular  lesions  in  the  lungs  are  compara- 
tively common  ;  deposits  of  recent  miliary  tubercle  in  the  peritoneum 
or  other  parts  occasionally  occur  ;  spinal  caries,  both  old  and  recent 
(healed  and  active),  is  present  in  a  certain  proportion  of  cases  ;  and 
inflammatory  deposits  or  abscesses  in  the  neighbourhood  of  the  capsules 
have  been  recorded  in  some  instances. 

The  spleen  is  sometimes  enlarged. 

The  stomach  often  contains  an  excess  of  mucus;  its  mucous 
membrane,  in  many  cases,  presents  a  mammillated  appearance,  and 
in  some  is  ecchymosed  or  even  superficially  ulcerated. 

The  solitary  glands  and  Peyer's  patches  are  usually  enlarged,  and 
the  glandular  structures  in  the  large  intestines  are  sometimes 
affected  in  the  same  manner.  Hyperaemia,  ecchymosis,  or  even 
superficial  ulceration  of  the  intestinal  mucous  membrane,  is  some- 
times present. 

These  changes  in  the  stomach  and  intestine  are  of  such  frequent 
■occurrence  that  they  can  hardly  be  regarded  merely  as  accidental 
or  associated  lesions  ;  they  are  perhaps  secondary  (trophic)  results 
of  the  (?  irritative)  alterations  in  the  abdominal  sympathetic,  which 
have  been  previously  described. 

The  muscles  are  in  some  cases  profoundly  atrophied. 

The  heart  is,  in  many  cases  of  Addison's  disease,  markedly 
atrophied.  I  have  been  very  much  impressed  by  the  smallness  of 
the  heart  in  more  than  one  case  which  I  have  examined.  The 
exact  cause  of  the  atrophy  of  the  heart  is  not  clear.  Possibly  it 
may  be  a  secondary  (trophic)  result  of  the  lesion  of  the  abdominal 
sympathetic  nerves  ;  possibly  the  suprarenal  capsules  may  be  con- 
cerned in  elaborating  some  substance  which  is  of  special  importance 
for  the  nutrition  of  the  heart  ;  or  possibly  the  vagi  nerves,  or  the 
cardiac  ganglia,  may  be  degenerated  or  diseased.  I  make  these 
suggestions  with  the  view  of  stimulating  investigation  ;  for  I  am 
disposed  to  think  that  the  atrophy  of  the  heart  is  a  feature  in  the 
pathology  of  Addison's  disease  which  has  not,  so  far,  received 
anything  like  the  degree  of  attention  which  it  deserves.  The 
observations  of  Schafer  and   Oliver,   which  were  made  after  this 


256  DISEASES   OF   THE   BLOOD   GLANDS. 

paragraph  was  written,  are  strongly  in  favour  of  the  view  that  the 
atrophy  of  the  heart  is  the  direct  result  of  suppression  of  the  func- 
tion of  the  suprarenal  glands  ;  in  other  words,  that  the  supra- 
renal glands  secrete  some  substance  which  exerts  an  active  influence 
on  the  nutrition  of  the  heart  (and  muscular  system). 

Changes  in  the  spinal  cord  (hyperaemia,  perivascular  exudations, 
collections  of  leucocytes  around  the  central  canal,  and  degenerative 
changes  in  the  nerve  cells  and  fibres,  have  been  described  in  a  few 
instances.  The  significance  of  such  alterations  and  their  relation, 
if  any,  to  the  disease  have  not  as  yet  been  definitely  determined. 

The  nature  of  the  capsular  lesion. — The  exact  pathological 
nature  of  the  fibro-caseous  change,  which  is  the  typical  and  charac- 
teristic lesion  of  Addison's  disease,  has  given  rise  to  much  discus- 
sion. It  has  usually  been  termed  scrofulous  or  tubercular,  but 
some  authorities,  doubting  its  tubercular  character,  have  described 
it  simply  as  inflammatory. 

In  my  opinion,  the  evidence  in  favour  of  the  tubercular  nature 
of  the  lesion  is  conclusive.  The  chief  facts  in  support  of  this  view 
are  : — 

Firstly,  That  in  many  of  the  cases  in  which  the  morbid  change 
is  not  too  far  advanced,  the  lesion  of  the  capsules  presents  all  the 
characters  of  a  tubercular  lesion.  Merkel,  for  example,  states  : — 
"  My  own  observations  have  shown  me,  in  cases  where  the  entire 
structure  has  not  been  broken  down  into  a  mass  of  detritus,  that  it 
consists  in  a  proliferation  of  small  cells,  lying  in  a  fine  reticulum, 
which  includes  giant-cells  in  great  numbers.  I  have  never,"  he 
says,  "  seen  any  appearance  which  so  forcibly  reminded  me  of 
Schueppel's  drawings  as  a  tuberculosis  of  the  suprarenal  capsules."  * 
Alezais  and  Arnaud,"j*  who  are  also  emphatic  as  to  the  tubercular 
character  of  the  lesion,  make  the  very  important  statement — and 
in  this  they  differ  from  almost  all  previous  observers — that  tubercle 
of  the  suprarenal  capsules,  whether  primary  or  secondary  to  tubercle 
in  other  organs,  is  usually  met  with  in  the  form  of  a  diffuse  tubercular 
infiltration,  rather  than  as  true  grey,  semi-transparent  granulations 
(miliary  tubercles). 

Secondly,  That,  in  a  considerable  number  of  cases,  tubercle 
bacilli  have  actually  been  demonstrated  in  the  diseased  capsules. 
It  is  perfectly  true  that  in  others — a  larger  number  of  cases — no 
tubercle  bacilli  could  be  detected  ;  but  in  the  examination  of  old 
f caseous  and  calcareous)  tubercular  lesions,  negative  results  are  of 

*  Ziemssen's  "  Cyclop.edia  of  Medicine,"  Vol.  viii.,  p.  651. 
t  "  Revue  de  Medecine,"  10th  April  J  891,  p.  289. 


ADDISON'S   DISEASE.  257 

comparatively  little  value.  In  such  conditions  one  positive  observa- 
tion (so  far  as  the  detection  of  the  tubercle  bacillus  is  concerned) 
is  of  much  greater  weight  than  several  negative  ones.  It  must,  too, 
be  remembered  that  the  opportunity  of  examining  the  capsules  in 
the  early  stages  of  the  lesion,  in  typical  cases  of  Addison's  disease, 
very  rarely  occurs.  It  is  probable,  I  think,  that  future  observa- 
tions will  show  that  the  tubercle  bacillus  is  usually  present  in  the 
early  stages  of  the  disease.  With  the  object  of  deciding  this  point, 
and  of  definitely  determining  whether  the  lesion  is  usually  tubercu- 
lar or  not,  the  presence  of  the  tubercle  bacillus  should  be  diligently 
and  carefully  looked  for  in  every  case  of  Addison's  disease  in 
which  the  capsular  lesion  is  in  an  early  stage  of  development.  I 
may  further  add,  that  the  search  for  the  tubercle  bacillus  should  not 
be  limited  to  the  capsules  themselves,  but  that  the  lymphatic 
glands  in  the  neighbourhood  of  the  capsules  should  also  be  care- 
fully examined. 

Thirdly,  Phthisis,  spinal  caries,  and  other  tubercular  lesions, 
such  as  recent  deposits  of  acute  miliary  tubercle  in  the  perito- 
neum, are  by  far  the  most  common  associated  lesions  which  are 
met  with  in  cases  of  Addison's  disease.* 

It  may  perhaps  be  objected  that  if  the  capsular  lesion  were 
tubercular,  other  evidences  of  tubercle  (in  the  form  of  secondary 
deposits)  ought  to  be  more  frequently  present.  This  argument  is, 
to  my  mind,  inconclusive.  It  is  probable,  I  think,  that  the  propor- 
tion of  cases  of  Addison's  disease,  in  which  associated  tubercular 
lesions  are  present,  is  as  great  as  in  the  case  of  other  localised 
tubercular  lesions  in  the  adult.  Even  in  cases  of  phthisis,  if  we 
exclude  those  secondary  lesions  which  are  obviously  due  to  direct 
infection  by  tubercular  sputum  (tubercular  deposits  in  the  larynx 
and  intestine),  and  the  glandular  and  other  lesions  which  result 
therefrom,  secondary  deposits  in  the  various  organs  of  the  body,  and 
generalised  (acute)  tuberculosis,  are  by  no  means  common.  Pos- 
sibly, too,  the  anatomical  structure  of  the  suprarenal  capsules,  and 
the  arrangement  of  their  lymphatics,  may  make  the  diffusion  of 
tubercular  processes,  which  originate  in  the  capsules,  more  difficult 
than  in  the  case  of  some  other  organs. 

Pathological  Physiology. 

The  manner  in  which  the  lesion  of  the  suprarenal  capsules 
produces  the  symptoms  of  Addison's  disease  has  given  rise  to  a 

*  The  lesion  of  the  stomach  and  intestine,  and  the  atrophy  of  the  heart, 
should,  in  my  opinion,  be  regarded  as  direct  results  of  the  disease,  rather 
than  mere  associated  lesions  or  complications. 

R 


258  DISEASES   OF   THE    BLOOD   GLANDS. 

vast  deal  of  discussion,  and  is  still  unsettled.  The  question  is  one 
of  great  difficulty  and  complexity  ;  in  the  present  state  of  our 
knowledge,  it  is  difficult  to  explain  all  the  facts  by  any  single 
hypothesis.  The  theory  which,  in  my  judgment,  is  by  far  the  most 
satisfactory,  is  that  which  supposes  (1)  that  the  lesion  of  the  cap- 
sules is  primary  ;  (2)  that  as  a  result  of  that  lesion  the  nervous 
structures  in  the  neighbourhood  of,  or  connected  with,  the  capsules 
are  in  many  cases  implicated  ;  and  (3)  that  the  symptoms  of  the 
disease  are  due  partly  to  suppression  of  the  function  of  the  supra- 
renal glands,  and  partly  to  the  associated  lesions  or  functional 
(irritative)  changes  in  the  nervous  structures  which  result  therefrom. 
Two  theories  have  been  advanced,  viz. : — 
The  Theory  of  the  Arrest  of  Suprarenal  Function. — That 
the  symptoms  of  Addison's  disease  are  due  to  destruction  of  the 
capsules — that  is,  to  abolition  of  the  functions  of  the  suprarenal 
bodies  or  suprarenal  glands,  as  they  may  be  termed. 

The  Nervous  Theory. — That  the  symptoms  of  Addison's 
disease  are  not  directly  due  to  destruction  of  the  suprarenal 
bodies,  but  that  they  result  from  the  derangements  in  the  abdo- 
minal sympathetic  and,  perhaps,  other  nervous  structures,  which 
the  lesion  of  the  suprarenal  capsules  produces. 

In  the  present  state  of  our  knowledge,  it  is  extremely  difficult 
to  reconcile  all  the  facts  in  accordance  with  either  one  or  other  of 
these  theories. 

In  favour  of  the  first  view,  are  the  facts  (a)  that  in  the  vast 
majority  of  cases  of  Addison's  disease  both  capsules  are  completely 
destroyed  ;  (b)  that  in  some  cases,  apparently  of  simple  atrophy  or 
fatty  change,  in  which  both  suprarenal  capsules  are  completely 
destroyed,  and  in  which,  so  far  as  post-mortem  examination  showed, 
there  was  no  lesion  of  the  abdominal  sympathetic,  typical  symp- 
toms of  Addison's  disease  are  nevertheless  developed  ;  and  (V)  that 
in  some  cases  of  Addison's  disease  the  administration  of  suprarenal 
extract  is  undoubtedly  attended  with  benefit. 

Against  this  view  are  :  (a)  The  fact  that  cancerous  destruction 
of  both  capsules  does  not  (except,  perhaps,  in  very  rare  instances) 
produce  the  symptoms  of  Addison's  disease  *  ;  (b)  that  in  many 
cases  of  Addison's  disease  there  is  strong  pathological  evidence  to 
show  that  the  suprarenal  capsules  have  been  completely  destroyed 
for  months  or  even  years  before  the  death  of  the  patient,  and  before 


*  The  question  is  whether  in  cases  of  cancerous  destruction  of  the  capsules, 
in  which  the  symptoms  of  Addison's  disease  were  present  during  life,  the  supra- 
renal glands  were  completely  destroyed. 


ADDISON  S   DISEASE.  259' 

the  symptoms  of  the  disease  were  developed  in  a  marked  degree  ; 
and  (V)  that  in  many  of  the  cases  of  this  kind  (cases  in  which  the 
capsules  are  completely  destroyed)  remarkable  temporary  improve- 
ment may  occur. 

In  favour  of  the  nervous  theory  of  the  disease  are  the  facts  :  (a) 
that  in  the  great  majority  of  cases  of  Addison's  disease  the  lesion 
is  one  and  the  same — a  fibro-caseous  (tubercular)  destruction  of 
both  capsules ;  (b)  that  cancerous  destruction  of  both  capsules- 
rarely  (in  the  opinion  of  some  authorities  never)  produces  the' 
symptoms  of  Addison's  disease  *  ;  (c)  that  in  rare  cases  one  capsule 
only,  or  (according  to  two  French  observers,  Drs  Alezais  and 
Arnaud)  a  part — the  peripheral  part — of  one  capsule  only  is  in- 
volved ;  (d)  that  in  almost  all  cases  of  Addison's  disease  the 
nerves  surrounding  the  capsules,  and  (in  many)  the  semilunar 
ganglia  and  large  nerve  cords  of  the  solar  plexus  are  embedded 
in  a  highly  irritative  (tubercular  and  inflammatory)  tissue  ;  (e)  that 
in  a  considerable  number  of  cases  naked-eye  and  microscopical 
changes  can  be  demonstrated  in  the  semilunar  ganglia  and  solar 
plexuses,  and  that  (according  to  Alezais  and  Arnaud)  microscopical 
alternations  are  always  present  in  the  pericapsular  ganglia  ;  (/") 
that  (according  to  Alezais  and  Arnaud)  in  some  cases  in  which  the 
tuberculosis  of  the  capsule  is  limited  to  the  centre  of  the  organ 
(that  is,  does  not  invade  the  cortical  portion),  and  in  which  the 
pericapsular  ganglia  and  the  abdominal  sympathetic  are  healthy, 
the  symptoms  of  Addison's  disease  are  not  developed ;  (g)  that  in 
a  few  rare  cases  in  which  the  symptoms  of  Addison's  disease  have 
been  present  during  life,  the  suprarenal  capsules  have  been  per- 
fectly healthy,  but  the  semilunar  plexus  and  solar  ganglia  have 
been  diseased  (enveloped  in  a  mass  of  new  growth) ;  (h)  that  in 
most  of  the  cases  of  Addison's  disease  in  which  suprarenal  extract 
has  been  administered  no  improvement  in  the  symptoms  has 
occurred. 

Against  this  view  (the  nervous  theory  of  the  disease)  are  : — 
(a)  That  in  many  cases  of  Addison's  disease  no  changes  have 
been  found  in  the  semilunar  ganglia  or  great  cords  of  the  solar  plexus. 
It  must,  however,  be  remembered,  that  the  nerve  fibres  which  are  in 

*  Possibly,  as  Dr  Robertson  has  suggested  (the  Goulstonian  Lectures  on 
the  Suprarenal  Bodies,  "British  Medical  Journal,"  30th  March  1895,  p.  680),  in 
such  cases  death  has  occurred  before  symptoms  characteristic  of  Addison's 
disease  have  had  time  to  develop  ;  or  "that  some  compensation  for  the  destruc- 
tion of  the  suprarenal  glands  is  present  in  accessory  suprarenal  bodies,  and 
that,  as  in  the  case  of  the  thyroid  gland,  symptoms  due  to  the  destruction  of 
the  main  glands  are  thus  avoided"  (loc.  cit.,  5th  April,  p.  746). 


260  DISEASES   OF   THE   BLOOD   GLANDS. 

the  immediate  neighbourhood  of  the  capsules,  are  probably  always 
involved  in  cases  in  which  the  typical  fibro-caseous  lesion  of  the 
capsules  is  present ;  and  that,  as  Dr  Dixon  Mann  has  pointed  out, 
it  is  quite  possible  that  an  irritation,  which  is  not  sufficiently 
marked  to  produce  visible  (naked-eye  or  microscopic)  changes, 
may  nevertheless  produce  very  marked  functional  disturbances  in 
the  nervous  system  ;  and  so  may  perhaps  produce  the  symptoms 
of  Addison's  disease.  Further,  Drs  Alezais  and  Arnaud,  as  I  have 
already  more  than  once  pointed  out,  claim  that  the  pericapsular 
ganglia  are  affected  in  all  cases  of  Addison's  disease*  though  they 
allow  that  in  many  cases  no  alterations  can  be  detected  in  the 
semilunar  ganglia  or  large  nerve  cords  of  the  solar  plexus. 

(b)  That  simple  atrophy  and  (as  my  case  seems  to  show)  fatty 
destruction  of  the  capsules  (independently  of  any  obvious  nervous 
irritation)  is  occasionally  the  cause  of  the  disease  ;  and 

(c)  That  in  some  cases  of  Addison's  disease — Case  IV.  is  one 
of  the  most  striking  which  has  as  yet  been  published — the  admini- 
stration of  suprarenal  extract  is  attended  with  marked  benefit. 

The  theory  that  the  symptoms  of  Addison's  disease  are  due  to 
arrested  or  defective  secretion  of  the  suprarenal  glands  is  un- 
doubtedly a  seductive  one,  and  the  knowledge  which  we  have 
obtained  during  the  past  few  years  regarding  the  important  influ- 
ence which  the  thyroid  and  other  ductless  glands  have  in  regulating 
the  metabolism  and  nutrition  of  the  tissues  renders  it  much  more 
probable  than  it  was  a  few  years  ago.  It  cannot,  I  think,  be 
lightly  put  aside.  As  I  have  stated  elsewhere,  it  is  not  improbable 
that  both  theories  (the  glandular  and  the  nervous)  are  correct.  It 
is  not  improbable,  I  think,  that,  while  some  of  the  symptoms  of 
Addison's  disease  are  the  direct  result  of  abolition  of  the  glandular 
function  of  the  suprarenal  capsules,  others  may  be  due  to  the 
secondary  lesions  in  the  abdominal  sympathetic,  which  the  primary 
lesion  in  the  suprarenal  capsules,  when  of  the  typical  fibro-caseous 
form,  seems  almost  always  to  be  associated  with.  Cases  such  as 
Cases  III.  and  IV.,  afford  strong  support  to  the  glandular  theory  of 
the  disease,  and  I  am  disposed  to  argue  more  strongly  in  favour  of 
this  theory  than  I  did  when  I  published  the  article  on  Addison's 
disease  in  1892^ 

Nevertheless,  for  the  reasons  already  given,  it  must,  I  think,  be 


*  It  is  probable  that  this  statement  only  holds  good  for  the  typical  (tuber- 
culous) cases.  There  is  no  reason  to  suppose,  in  cases  of  simple  fibrous  atrophy, 
apparent  absence,  or  fatty  transformation  (the  condition  which  seems  to  have 
been  present  in  Case  IV.),  that  the  pericapsular  ganglia  are  affected. 

t  "Atlas  of  Clinical  Medicine,"  Vol.  i.,  p.  69. 


ADDISON'S   DISEASE.  261 

allowed  that  in  most  cases  of  Addison's  disease  the  lesions  in  the 
abdominal  sympathetic  play,  at  all  events,  some  part,  and  probably 
an  important  part,  in  the  production  of  some  of  the  symptoms. 
The  facts  (a)  that  in  some  rare  cases  in  which  the  characteristic 
pigmentation  and  some  of  the  other  constitutional  symptoms  of  the 
disease  were  present  during  life,  the  suprarenal  capsules  were 
found  to  be  healthy  after  death,  while  the  abdominal  sympathetic 
was  involved  in  a  mass  of  new  growth  ;  and  (b)  that  in  the  great 
majority  of  the  cases  which  have  been  recorded  in  which  both 
suprarenal  capsules  were  completely  destroyed  by  malignant 
deposits  there  were  no  symptoms  of  Addison's  disease,  are  extremely 
difficult  to  reconcile  with  the  purely  and  exclusively  glandular 
origin  of  the  disease. 

The  theory  that  the  symptoms  of  Addison's  disease  and  the 
lesion  of  the  suprarenal  capsules  are  both  due  to  a  primary 
lesion  of  the  abdominal  sympathetic. — This  view,  which,  so  far  as 
I  know,  was  first  suggested  by  Professor  Semmola  of  Naples,  to 
account  for  all  cases  of  Addison's  disease,  and  which  has  also  been 
advanced  by  Dr  Sydney  Coupland  to  explain  those  rare  cases  in 
which  the  symptoms  of  Addison's  disease  appear  to  result  from  a 
simple  atrophy  of  the  capsules,  has,  so  far  as  I  know,  no  positive 
facts  to  support  it. 

It  is  impossible,  I  think,  to  conceive  that  the  ordinary  fibro- 
caseous  (tubercular)  lesion  of  the  capsules  is  in  all  cases  of  Addison's 
disease  a  secondary  (trophic)  result  of  a  lesion  of  the  ganglionic 
nerve  centres,  as  Professor  Semmola  suggests  ;  and  Dr  Coupland's 
limitation  of  the  theory,  though  more  plausible,  could  only, 
I  think,  be  provisionally  accepted,  as  a  mere  temporary  working 
hypothesis  (for,  so  far  as  I  know,  there  are  no  positive  facts  to 
support  it),  if  it  were  allowed — and  this  I  am  not  prepared  to 
admit — that  the  other  theories  advanced  above  have  completely 
failed  to  afford  a  reasonable  explanation  of  the  facts.  I  am  firmly 
of  opinion  that  in  the  vast  majority  of  cases  of  Addison's  disease, 
in  the  ordinary  typical  cases  at  all  events,  the  capsular  lesion  is 
primary,  and  that  the  alterations  in  the  nervous  structures  are 
secondary. 

The  exact  mode  of  production  of  the  pigmentation  of  the 
skin  has  not  as  yet  been  determined.  One  view  is  that  it  is  due  to 
an  increased  supply  of  blood  pigment,  and  another  that  it  is  a 
trophic  change  the  result  of  perverted  innervation.  The  former 
view  is,  I  think,  the  more  probable,  for  it  is  extremely  difficult  to 
account  for  the  pigmentation  of  the  mucous  membranes  on  the 
latter  supposition. 


262  DISEASES   OF   PHE   BLOOD   GLANDS. 

Dr  M'Munn  believes  that  "the  adrenals  remove  from  the  cir- 
culation useless  and  worn-out  pigments  and  their  accompanying 
proteids;"  and  that  "when  the  adrenals  are  diseased,  these  effete 
pigments  and  effete  proteids  circulate  in  the  blood  ;  the  former,  or 
their  incomplete  metabolites,  producing  pigmentation  of  skin  and 
mucous  membrane  and  appearing  often  in  the  urine  as  uro-hsemato- 
porphyrin,  the  latter  producing  toxic  effects,  and  leading  to  further 
deterioration  of  the  blood,  with  its  consequences."  * 

Prognosis. 

The  prognosis  in  Addison's  disease  is  most  unfavourable. 
Almost  all  cases  terminate  sooner  or  later  in  death  ;  this  is  the 
experience  of  all  observers.  Very  few  cases  have  been  reported  in 
which  recovery  has  taken  place.  At  the  International  Medical 
Congress  of  London,  Sir  William  Gull  related  the  case  of  a  man, 
aged  51,  who  had  presented  all  the  characteristic  symptoms  of  the 
disease,  in  which  complete  recovery  had  taken  place,  f  Dr  Finny  has 
also  recorded  a  case  in  which  the  symptoms  were  typical,  the  pigmen- 
tation affecting  not  only  the  skin  but  the  buccal  mucous  membrane, 
in  which  there  was  a  complete  absence  of  any  other  discoverable 
disease  or  local  lesion  to  account  for  the  condition,  in  which  the 
symptoms,  including  the  discoloration  of  the  skin,  disappeared 
under  treatment,  and  the  patient  eventually  got  well.  J  In  one  of 
my  own  cases  (Case  XL),  in  which,  however,  I  admit  that  the 
diagnosis  was  not  perhaps  absolutely  clear,  though  the  balance  of 
evidence  seems  to  me  strongly  in  favour  of  Addison's  disease, 
complete  recovery  also  took  place. 

Seeing  that  tubercular  lesions  in  other  parts  of  the  body  are  so 
frequently  arrested  and  recovered  from,  it  is  not  improbable  that  if 
we  could  recognise  and  actively  treat  the  lesion  in  its  early  and 
presumably  curative  stage,  recovery  might  more  frequently  occur. 
Unfortunately,  there  is  reason  to  suppose  that  in  most  cases  of  the 
disease  the  lesion  is  already  far  advanced,  and  that,  in  some,  the 
suprarenal  capsules  are  completely  destroyed  before  the  symptoms 
become  sufficiently  pronounced  to  lead  the  patient  to  consult  a 
doctor. 

Complete  destruction  of  the  capsules  is,  as  we  have  already  seen, 
not    necessarily   fatal ;    and   there  are,   I   think,  good  grounds  for 

*  "British  Medical  Journal,"  4th  February  18S8,  p.  233. 

t  "Transactions  of  the  International  Medical  Congress  of  London,"  Vol.  ii., 

P-  75- 

I  "Dublin  Medical  Journal,"  1882,  p.  293. 


ADDISON'S   DISEASE.  263 

supposing  that  the  prognosis,  as  regards  the  duration  of  life,  is  more 
favourable  than  is  generally  believed.  In  hospital  patients,  the 
average  duration  of  life  after  the  symptoms  of  Addison's  disease 
have  developed  sufficiently  to  be  recognised  and  to  necessitate  the 
patients  taking  medical  advice,  is  probably,  at  the  most,  two  years. 
In  those  cases  in  which  the  patient  is  more  favourably  circum- 
stanced, in  which  he  is  able  to  carefully  protect  himself  from  all 
causes  of  depression,  and  in  which  the  exacerbations  of  the  disease 
are  carefully  and  intelligently  treated,  the  prognosis,  as  regards  the 
mere  duration  of  life,  is  probably  more  favourable. 

Treatment. 

If  Addison's  disease  is,  in  the  great  majority  of  cases,  due 
to  tuberculosis  of  the  capsules,  it  is  obvious  that  the  first  indi- 
cation for  treatment  is  to  cure  the  tubercular  condition  of  the 
capsules,  or  to  remove  the  diseased  glands  by  means  of  operation. 
Successful  excision  of  the  suprarenal  capsules,  or  rather  of  one 
suprarenal  capsule,  has,  so  far  as  I  know,  only  once  been  per- 
formed in  the  human  subject ;  and  although  it  would  be  rash 
in  the  extreme  in  these  days  of  brilliant  surgical  achievement 
to  affirm  that  the  operation  cannot  be  safely  and  satisfactorily 
performed,  yet  it  may,  I  think  (in  the  present  state  of  our  know- 
ledge), with  confidence  be  stated  that,  in  such  a  disease  as  Addi- 
son's disease,  in  which  even  trivial  causes  are  apt  to  be  followed 
by  the  most  profound  and  even  fatal  prostration  and  collapse,  the 
risks  of  the  operation  are  so  great  as  to  render  the  operation  one 
of  extreme  danger,  in  the  great  majority  of  cases  at  all  events. 

Further,  there  is,  as  we  have  seen,  good  reason  to  suppose  that 
in  many  cases  the  lesion  is  already  so  far  advanced  that  the 
capsules  are  to  all  intents  and  purposes  destroyed  at  the  time 
when  the  patient  first  comes  under  observation.  In  such  cases, 
all  treatment,  so  far  as  the  capsules  themselves  are  concerned, 
is,  of  course,  utterly  useless. 

Fortunately,  in  the  adult  at  all  events,  the  suprarenal  capsules 
do  not  seem  to  be  essential  for  life.  There  is  good  reason  to 
believe  that  in  many  cases  of  Addison's  disease,  life  is  prolonged 
for  months,  perhaps  even  for  years,  after  the  capsules  have  been 
completely  destroyed  and  entirely  converted  into  caseo-calcareous 
masses,  provided  always  (1)  that  there  is  no  progressive  lesion  in 
the  surrounding  nerves  ;  (2)  that  all  sources  of  active  irritation  in 
the  neighbourhood  of  the  solar  plexuses  have  been  removed  ;  (3) 
that   the    patient  is  carefully  protected   from   all  depressing  and 


264  DISEASES   OF   THE    BLOOD   GLANDS. 

injurious  external  conditions ;  and  (4)  that  there  are  no  other 
lesions  in  the  body.  I  see  no  reason  why  life  should  not  be  pro- 
longed under  such  circumstances  for  (to  speak  cautiously)  a  very 
considerable  period  of  time. 

General  Treatment. — In  the  early  stages  of  the  case,  and 
granting  that  the  view  which  has  been  advocated  above  is  correct, 
viz.,  that  in  the  vast  majority  of  cases  of  Addison's  disease  the 
capsular  lesion  is  tubercular,  the  same  measures  should  be  adopted 
as  are  useful  in  the  treatment  of  tubercular  lesions  elsewhere. 
Koch's  plan  of  treatment — -whatever  value  it  may  ultimately  be 
proved  to  have  in  phthisis  and  the  tubercular  lesions  of  some  other 
organs — is,  I  consider,  absolutely  unjustifiable  here.  The  violent 
constitutional  reaction  which  it  is  apt  to  produce  would  in  all 
probability  kill  a  patient  affected  with  well-marked  or  advanced 
Addison's  disease. 

At  every  stage  of  the  disease,  the  most  careful  precautions 
should  be  taken  to  prevent  gastro-intestinal  irritation,  to  allay  such 
irritation  when  it  does  arise,  and  to  protect  the  patient  from  every- 
thing which  is  calculated  (in  him)  to  produce  exhaustion  and 
depression.  In  hospital  cases,  it  is  especially  important  to  take 
care  that  the  patient  is  not  "over-examined."  In  one  of  Dr 
Greenhow's  patients,  the  mere  fatigue  of  being  submitted  to  care- 
ful examination  in  bed,  on  several  occasions  brought  on  paroxysms 
of  retching,  sickness,  hiccough,  and  intense  temporary  depression. 

It  is  essential,  both  with  the  object  of  endeavouring  to  cure  the 
tubercular  lesion  of  the  capsules,  in  its  early  and  curable  stages, 
and  with  the  object  of  prolonging  life  after  the  capsules  have  been 
destroyed,  to  maintain  the  general  health  in  the  highest  possible 
state  of  efficiency.  The  patient  should,  if  possible,  be  well  housed, 
well  clothed,  and  carefully  fed.  Protection  from  cold  and  all  causes 
of  bodily  fatigue  and  mental  excitement  is  essential.  It  may  be 
confidently  affirmed  that  a  laborious  occupation  is,  in  Addison's 
disease,  incompatible  with  the  prolongation  of  life.  The  diet  should 
consist  chiefly  of  milk,  butter,  eggs,  farinaceous  foods,  fish,  and 
white  meats  ;  in  some  cases,  the  patient  has  an  actual  distaste  for  red 
Tbutcher)  meat,  and  this  indication  on  the  part  of  nature  should  be 
borne  in  mind..  Well-cooked  potatoes  and  tender,  well-cooked 
vegetables  may  be  allowed  in  small  quantities  unless  they  appear 
to  disagree. 

Small  quantities  of  alcoholic  stimulant  seem,  in  many  cases, 
more  especially  when  the  prostration  and  exhaustion  are  extreme, 
to  be  beneficial. 

Drastic  purgatives  should  never  be  prescribed  ;  when  there  is 


ADDISON'S   DISEASE.  265 

constipation,  the  bowels  should,  if  possible,  be  regulated  by  diet ; 
or,  if  this  is  ineffectual,  an  enema  or  a  small  dose  of  a  mild  laxative 
should  be  cautiously  employed. 

Cod-liver  oil  should  be  given  in  those  cases  in  which  it  is  well 
borne  ;  in  those  cases  in  which  it  is  satisfactorily  assimilated,  and 
in  which  it  does  not  produce  nausea  and  sickness,  it  is,  without 
doubt,  eminently  useful ;  unfortunately  in  many  cases  it  is  not 
well  borne.  Dr  Greenhow  states  that  cod-liver  oil  did  not  agree 
well  with  any  of  the  patients  who  were  under  his  care  for  Addison's 
disease.  Glycerine,  in  doses  of  two  drachms,  given  two  or  three 
times  a  day,  in  conjunction  with  either  the  citrate  or  the  tincture 
of  the  perchloricle  of  iron,  seemed  to  him  to  be  more  effectual  than 
any  other  medicine  for  keeping  up  the  general  health  and  strength. 

The  syrup  of  the  iodide  of  iron,  arsenic,  and  strychnine  are 
some  of  the  most  useful  drug  remedies.  But  here  again — -and  the 
caution  applies  especially  to  arsenic — caution  in  administration  is 
necessary.  Until  the  physician  is  assured  that  the  drug  is  well 
borne,  small  doses  only,  carefully  and  gradually  increased,  should 
be  prescribed. 

Mild  counter-irritation  over  the  position  of  the  suprarenal 
capsules  is  probably  beneficial.  Painting  with  tincture  of  iodine  is 
the  method  which  I  am  in  the  habit  of  employing. 

During  the  paroxysmal  exacerbations  of  the  disease,  and  in 
advanced  stages  when  the  asthenia  is  marked,  the  patient  should 
be  confined  to  bed  ;  further,  he  should  be  warned  against  rising 
suddenly  from  the  recumbent  position  and  making  any  sudden 
effort. 

Vomiting  and  diarrhcea,  when  they  occur,  must  be  carefully 
treated.  For  the  relief  of  vomiting,  a  mustard  blister  to  the  pit  of 
the  epigastrium,  small  doses  of  morphia,  either  hypodermically  or 
by  the  stomach,  bismuth,  hydrocyanic  acid,  creasote  or  carbolic 
acid,  with  small  quantities  of  champagne  or  brandy,  ice  and  appro- 
priate food  (milk,  or  milk  and  lime-water,  in  small  quantities, 
frequently  repeated),  are  perhaps  the  most  useful  measures. 

Complications  and  associated  lesions,  such  as  phthisis  and 
caries  of  the  spine,  must,  of  course,  be  treated  in  accordance  with 
their  exact  nature ;  but  in  dealing  with  these  conditions,  the 
physician  must  always  remember  that  the  patient  is  suffering  from 
Addison's  'disease. 

Specific  Treatment. — There  seems  good  reason  to  believe  that 
some  of  the  symptoms  of  Addison's  disease  at  all  events  (some 
authorities  advocate  the  view  that  all  of  the  symptoms  of  the 
disease)  are  due  to  defective  suprarenal  secretion,  i.e.,  to  destruction 


266  DISEASES   OF   THE   BLOOD   GLANDS. 

of  the  suprarenal  glands  and  abolition  of  the  suprarenal  function. 
Now  if  this  view  of  the  pathology  of  the  disease  is  correct,  the 
specific  treatment  of  the  disease — the  administration  of  suprarenal 
extract — ought  to  produce  benefit  and  ought  to  remove  the 
symptoms  of  the  disease,  just  as  the  administration  of  thyroid 
extract  produces  such  marked  benefit  and  removes  the  symptoms 
of  the  disease  in  cases  of  myxcedema.  And  as  a  matter  of  fact 
this  is  sometimes  the  case.  In  Case  IV.  of  my  series  most  marked 
benefit  undoubtedly  resulted  from  the  administration  of  the  remedy; 
and  other  cases  have  been  reported  in  which  a  beneficial  result  has 
been  produced.  But  such  cases  appear  to  be  exceptional.  It  must, 
I  think,  be  allowed,  so  far  as  our  present  information  enables  us  to 
judge,  that  it  is  only  in  a  small  proportion  of  cases  of  Addison's 
disease  that  the  administration  of  suprarenal  extract  produces  any 
marked  benefit.  This  is  perhaps  due  to  the  facts  (i)  that  in 
Addison's  disease  the  lesion  is  tubercular,  and  (2)  that  some  of  the 
symptoms  of  the  disease  are  due,  not  to  suppression  of  the  func- 
tion of  the  suprarenal  gland,  but  to  the  associated  secondary  lesions 
which  are  produced  in  the  abdominal  sympathetic.  In  those  cases 
of  Addison's  disease  (such  as  Cases  III.  and  IV.)  in  which  the 
function  of  the  suprarenal  glands  is  simply  suppressed,  and  in 
which  there  is  no  tubercular  lesion  and  no  involvement  of  (lesions  in) 
the  abdominal  sympathetic  {i.e.,  in  which  there  is  simple  fibrous 
atrophy  of  the  capsules,  in  which  the  capsules  are  replaced  by  fat, 
or  are  congenitally  absent),  the  administration  of  suprarenal  extract 
would  a  priori  be  expected  to  produce  more  marked  benefit  than 
in  those  cases  of  Addison's  disease  in  which  the  lesion  of  the 
capsules  is  tubercular  and  in  which  the  abdominal  sympathetic  is 
extensively  involved.  I  may,  perhaps,  make  my  meaning  more 
clear  by  saying,  that  if  the  thyroid  body  were  completely  destroyed 
by  a  tubercular  lesion,  symptoms  of  myxcedema  would  result ;  but 
that  in  cases  of  complete  tubercular  destruction  of  the  thyroid  gland 
(if  such  a  condition  occurs),  the  results  of  thyroid  treatment  would 
in  all  probability  be  less  satisfactory  than  in  the  ordinary  everyday 
cases  of  myxcedema,  in  which  the  tissue  of  the  thyroid  gland  is 
simply  destroyed  by  a  process  of  cirrhotic  atrophy. 

Now  in  typical  cases  of  Addison's  disease  there  is  not  only  a 
tubercular  lesion  and  abolition  of  the  function  of  the  suprarenal 
capsules,  but  there  is  associated  disease  of  the  abdominal  sym- 
pathetic. Hence  perhaps  the  explanation  of  the  fact  that  while 
thyroid  extract  speedily  cures  myxcedema,  suprarenal  extract  does 
not  as  a  rule  produce  marked  benefit  in  cases  of  Addison's  disease. 

These  therapeutic  considerations  lend,  I   think,  additional  sup- 


ADDISON'S   DISEASE.  267 

port  to  the  theory  which  I  have  for  long  advocated,  that  some  of 
the  symptoms  of  typical  (tubercular)  cases  of  Addison's  disease  are 
probably  due  to  the  tubercular  character  of  the  lesion  and  to  the 
associated  disease  in  the  abdominal  sympathetic,  which  the  tuber- 
cular lesion  in  the  capsules  seems  almost  invariably  to  produce, 
while  others  are  the  result  of  abolition  of  the  function  of  the  supra- 
renal glands. 

The  suprarenal  extract  may  be  administered  either  in  the  form 
of  a  liquid  extract  or  of  compressed  tabloids  ;  or  the  raw  gland, 
finely  minced  and  given  in  rice  paper,  or  mixed  with  some 
article  of  food,  may  be  given.  The  suprarenal  extract  seems  to 
pass  undestroyed  through  the  stomach  ;  consequently  the  hypo- 
dermic method  has  no  advantage,  and  has  distinct  disadvantages 
(risk  of  sepsis,  greater  difficulty  of  administration,  etc.),  over  the 
method  of  administration  by  the  stomach.  In  Case  IV.  the 
raw  gland  produced  irritation  of  the  stomach  and  vomiting ; 
the  liquid  extract  (ten  drops  three  times  daily)  agreed  perfectly. 
In  a  case  which  I  have  at  present  under  observation,  the  patient 
.at  first  took  ten  drops  of  Brady  &  Martin's  liquid  extract  three 
times  daily ;  recently,  this  dose  has  been  increased  to  twenty  drops 
three  times  daily,  and  I  intend  to  still  further  increase  the  dose,  if 
the  remedy  continues  to  be  well  borne.  In  this  case  (Case  VI.) 
sufficient  time  has  not  as  yet  elapsed  to  enable  me  to  say  whether 
the  remedy  is  likely  to  be  beneficial  or  not ;  but  the  patient's  mother 
states  most  emphatically  that,  since  the  treatment  was  commenced, 
six  weeks  ago,  the  debility  and  prostration  which  were,  in  addition 
to  the  pigmentation,  the  only  symptoms,  have  been  decidedly 
less  marked.  As  yet,  no  perceptible  change  in  the  pigmentation 
has  taken  place. 


Illustrative  Cases  of  Addison's  Disease  observed  by  the 
Author  during  life. 

CASE  I.  —  Typical  Addison's  Disease  of  At  Least  Ten  Years'  Duration; 
Excessive  Languor  and  Debility  j  Feeblettess  of  the  Heart's  Action  ;  No 
Emaciation ;  Extreme  Pigme?itation  of  the  Skin  and  Buccal  Miccoics 
Membrane  ;  Pearliness  of  the  Conjunctives ;  Some  Ancemia;  Paroxysmal 
Exacerbations  of  the  Languor  a?td  Debility ;  Attacks  of  Vomiting  ; 
Occasional  Hiccough  j  Great  Susceptibility  to  Cold ;  Deeply  Pigme?ited 
Lupoid  Patches  on  the  Abdomen.    Death.    No  Post-mortem  Examination. 

Female,  aged  26,  seen  in  consultation  in  May  1886. 

Complaints. — Extreme  weakness  and  prostration,  paroxysmal  attacks  of 
vomiting,  pigmentation  of  the  skin. 

Duration. — At  least  four,  and  probably  eight,  years. 


268  DISEASES   OF   THE   BLOOD   GLANDS. 

Previous  History. — Until  eight  or  nine  years  ago  the  patient  enjoyed  good 
health,  and  was  active  and  well  nourished.  At  that  time,  she  became  languid 
and  debilitated  without  obvious  cause.  The  debility  developed  very  gradually 
and  insidiously.  For  the  past  four  years,  it  has  been  much  more  marked. 
Some  months  after  the  debility  developed,  her  friends  noticed  that  the  skin  was 
becoming  darker  ;  the  pigmentation  was  first  noticed  on  the  face  and  back  of 
the  hands,  especially  over  the  knuckles.  As  a  young  girl  she  had  a  white  skin 
and  fine  clear  complexion,  though  her  hair  and  eyes  are  naturally  dark. 

During  the  second  year  of  her  illness,  the  asthenia  and  pigmentation 
gradually  increased  ;  the  weakness  and  feeling  of  languor  and  depression  were 
at  times  extreme  ;  the  pigmentation  gradually  extended  over  the  whole  body, 
and  became  much  darker  in  colour  ;  attacks  of  vomiting",  which  usually  lasted 
several  days  at  a  time,  and  which  used  to  render  her  completely  prostrate,  now 
frequently  occurred  ;  the  appetite  failed  ;  she  became  short  of  breath,  suffered 
from  palpitation  on  exertion,  and  was  giddy  on  stooping  or  rising  suddenly  from 
the  recumbent  to  the  erect  position  ;  the  menstruation,  which  had  previously 
been  regular  and  natural,  now  became  scanty  and  irregular,  and  at  times  dis- 
appeared for  months  together. 

During  the  first  four  or  five  years  of  her  illness,  she  remained  plump  and 
fat ;  during  the  past  three  or  four  years,  she  has  got  decidedly  thinner,  but  she 
is  still  well  nourished. 

She  has  not  had  any  pains  in  the  abdomen  or  back,  and  she  has  not  suffered 
from  diarrhoea. 

For  several  years  past  she  has  kept  indoors,  and  for  the  most  part  has 
remained  in  her  own  room,  during  the  winter  months. 

During  the  past  autumn  and  winter  (1889),  she  was  in  the  house  for  eight 
months — never  once  out  of  doors  during  the  whole  of  that  time  ;  she  always 
feels  worse  during  the  winter,  but  picks  up  again  during  the  summer  ;  she  does 
not  get  up  until  11  A.M.,  and  takes  the  greatest  care  of  herself  in  every  way. 
Since  her  illness  commenced  she  has  been  very  susceptible  to  cold,  and  very 
easily  upset  by  the  slightest  excitement  or  exertion. 

Family  History. — The  patient  is  one  of  five  children  ;  one  died  at  the  age  of 
4^  years  of  "water  in  the  head"  ;  the  other  three  (boys),  aged  22,  19  and  13 
respectively,  have  all  been  "  terribly  troubled  with  their  stomachs  "  ;  as  a  child, 
the  youngest  suffered  very  much  from  "  enlarged  glands  in  the  neck." 

Her  father  died  at  the  age  of  37,  of  heart  disease,  complicated  with  pleurisy 
and  disease  of  the  liver.  Her  mother  is  a  strong',  healthy,  active  woman, 
aged  5 1 . 

So  far  as  is  known,  none  of  either  her  father's  or  her  mother's  relatives  have 
died  from  consumption. 

There  is  no  "black  blood"  in  the  family. 

Present  Condition. — The  patient  is  a  bright,  intelligent  young  woman.  She 
looks  more  like  a  mulatto  than  a  European.  The  skin  of  the  face  and  body 
generally  is  of  a  dark  brown  colour  ;  the  contrast  between  the  dark  brown  face 
and  the  white  pearly  conjunctiva  is  most  striking-. 

Her  chief,  in  fact  her  only,  complaint  is  a  feeling  of  excessive  languor  and 
debility  ;  she  says  that  she  is  easily  fatigued  and  exhausted,  and  that  she  is 
unequal  for  any  sustained  effort  either  of  body  or  mind.  The  feeling  of  tired- 
ness and  debility  are  much  greater  at  times  than  at  others  ;  during  the  periods 
of  increased  exhaustion  (paroxysmal  exacerbations  of  the  disease)  she  feels 
"  terribly  languid  "  and  depressed  in  mind,  as  well  as  fatigued  in  body.     She  is 


ADDISON'S   DISEASE.  269 

naturally  of  a  cheerful  disposition,  and  rapidly  picks  up  and  regains  her  spirits 
after  the  temporary  exacerbations  of  the  languor  and  depression  pass  away. 
During  the  past  winter  (1889)  she  has  felt  less  languid  than  she  did  for  some 
years  previously. 

Though  distinctly  thinner  than  she  was  a  few  years  ago,  she  is  well  nourished  ; 
the  limbs  are  rounded,  the  breasts  plump  and  well  developed,  and  the  body 
well  covered  with  fat. 

The  pulse  is  remarkably  small  and  weak  ;  it  is  usually  somewhat  quick, 
ranging  from  84  to  108. 

The  heart's  impulse  is  imperceptible,  and  the  heart-sounds  are  feeble,  the 
first  sound  in  particular  being  short  and  faint  ;  there  is,  however,  no  evidence 
of  cardiac  or  vascular  disease.  Palpitation  is  readily  induced  either  by  excite- 
ment or  exertion  ;  the  slightest  effort  makes  the  patient  feel  short  of  breath  ;  she 
occasionally  feels  faint  ;  she  is  giddy  when  she  stoops,  looks  up  to  the  ceiling, 
or  suddenly  rises  from  the  recumbent  to  the  erect  position.  She  takes  great 
care  to  avoid  any  exertion  or  excitement  ;  she  never  walks  quickly  ;  she  lives  on 
the  ground-floor,  and  never  attempts  to  go  upstairs. 

The  appetite,  though  still  small,  is  better  than  it  used  to  be  a  year  or  two 
ago  ;  she  rarely  eats  butcher- meat,  and  lives  chiefly  on  milk,  water,  bread,  and 
butter  ;  her  digestion  is  good,  and  the  bowels  regular ;  as  has  been  previously 
stated,  she  has  not,  during  the  whole  course  of  her  illness,  suffered  from 
diarrhoea.  For  the  past  year  she  has  been  almost  entirely  free  from  the 
periodical  attacks  of  vomiting,  which  were  of  frequent  occurrence  during  the 
earlier  periods  of  her  illness,  and  which  used  to  exhaust  her  terribly.  She 
occasionally  suffers  from  hiccough.  Her  teeth  are  very  bad,  but  they  do  not 
ache  and  do  not  cause  her  any  trouble.  Her  tongue  is  clean  and  moist,  but 
deeply  pigmented,  as  will  be  presently  described. 

The  pigmentation  affects  the  skin  of  the  whole  body  ;  in  certain  situations 
the  colour  is  much  darker  than  in  others.  The  areolae  of  the  nipples,  the  nipples 
themselves,  and  the  sides  of  the  abdomen  about  the  waist  (lumbar  regions),  are 
very  dark  ;  a  dark  brown  line  extends  from  the  pubes  towards  the  umbilicus, 
but  the  skin  around  the  umbilicus  is  not  more  deeply  pigmented  than  that  of  the 
rest  of  the  abdomen  ;  the  skin  of  the  face,  back  of  the  hands,  and  front  folds  of 
the  axillae,  is  very  dark  brown  (walnut -juice  coloured) ;  the  lower  extremities  are 
less  deeply  stained  than  the  abdomen  and  back  ;  the  palms  of  the  hands  and 
the  soles  of  the  feet  are  the  parts  which  are  least  pigmented ;  but  even  in  these 
situations  the  skin  is  uniformly  stained  of  a  pale  golden-brown  colour. 

The  pigmentation  varies  in  depth  from  time  to  time,  and  is  increased  during 
the  menstrual  period. 

The  skin,  generally  speaking,  is  beautifully  smooth,  soft,  elastic,  and  pliable. 
The  odour  of  the  skin  is  in  no  way  remarkable. 

The  scalp  is  dry,  rough,  and  thickly  covered  with  furfuraceous  scales 
(pityriasis). 

Three  lupoid-like  patches,  which  measure  from  I  to  1  inch  in  length,  and 
from  j  to  5  an  inch  in  breadth,  are  situated  over  the  lower  part  of  the  abdomen  ; 
there  is  also  a  similar  patch  in  the  left  groin.  All  of  these  lupoid  patches  are 
very  deeply  pigmented — almost  black ;  the  patient  says  they  have  been  present 
for  about  a  year  ;  they  do  not  itch,  and  do  not  give  her  any  inconvenience 
whatever. 

The  lips,  gums,  tongue,  and  buccal  mucous  membrane  are  all  pigmented. 

On  the  lips,  the  pigment  deposits  are  situated  along  the  commissure  (the  line 


270  DISEASES   OF   THE   BLOOD   GLANDS. 

of  contact  of  the  lips  when  the  mouth  is  closed)  ;  they  are  bluish-black  in  colour,, 
and  remind  one  of  ink-stains,  or  stains  produced  by  blackberry  juice. 

On  the  gums,  the  pigmentary  deposits  are  of  the  same  colour  as  on  the 
lips  ;  they  are  situated  on  the  outer  surface  of  the  gums,  chiefly  at,  and 
immediately  below,  the  insertion  of  the  incisor  teeth  ;  the  gums  are  of  a  deep 
red  colour. 

On  the  buccal  mucous  membrane,  the  pigmentary  deposits  are  not  numerous  ;. 
they  are  of  a  dirty  brown  (not  a  bluish-black)  colour  ;  and  are  situated  opposite 
the  line  of  junction  of  the  closed  teeth,  i.e.,  along  a  line  drawn  horizontally 
backwards  from  the  angle  of  the  mouth. 

On  the  tongue,  the  pigmentary  deposits  are  unusually  well  marked  ;  they  are 
of  a  bluish-black  (blackberry  juice)  colour,  rather  more  blue  and  not  quite  so 
black  as  the  deposits  on  the  lips  and  gums  ;  they  are  chiefly  situated  on  the 
dorsum  of  the  tongue  near  the  root,  a  situation  which,  according  to  Dr 
Greenhow,  is  exceptional.  Under  the  tongue,  and  distributed  on  each  side 
along  the  course  of  lingual  arteries,  there  are  several  small  deposits  of  pigment 
of  a  rich  golden-brown  colour  ;  they  appear  to  be  adhering  to  the  outer  coats 
of  the  vessels,  and  are  only  seen  along  the  line  of  the  lingual  arteries. 

The  fundus  oculi  seemed  to  me  to  be  more  deeply  pigmented  than  normal, 
but  Mr  George  Berry,  who  very  kindly  saw  the  patient  with  me,  did  not  think 
that  this  was  the  case. 

Though  the  conjunctiva?  are  so  white  and  pearly,  the  patient  is  not  pro- 
foundly anaemic.  The  lips,  gums,  and  tongue  are  all  well,  in  fact  deeply, 
coloured  ;  while  the  buccal  mucous  membrane  covering  the  cheeks,  the  con- 
junctiva covering  the  lower  lids,  as  well  as  the  portions  of  the  membrane 
which  cover  the  sclerotic,  and  the  nails,  are  distinctly  paler  than  normal.  A 
drop  of  blood  obtained  by  pricking  the  finger  was  very  deeply  coloured — a  dark 
claret  colour.  The  red  corpuscles  numbered  (average  of  several  counts) 
3,250,000  and  the  haemoglobin  =  80  percent.;  consequently,  the  colour  index, 
after  correction  (allowing  for  the  low  reading  of  Gower's  instrument)  is  above 
the  normal,  and  equals  1.2  ;  the  white  corpuscles  are  not  in  excess.  The  red 
corpuscles  form  rouleaux,  and  are  quite  normal  in  size  and  shape.  No  free 
pigment  granules  were  detected  in  the  blood. 

The  urine  is  copious  (80  oz.  in  24  hours),  very  pale,  slightly  acid,  specific 
gravity  1012,  no  albumen,  urea  =  400  grains  in  24  hours. 

For  the  past  few  years,  the  patient  has  menstruated  more  or  less  irregularly 
during  the  winter,  and  has  ceased  to  menstruate  altogether  during  the  summer. 
On  13th  September  1890,  she  began  to  menstruate  for  the  first  time  for  several 
months. 

The  patient  sleeps  remarkably  well  ;  she  generally  goes  to  sleep  at  10  and 
is  wakened  at  8  o'clock  ;  her  aunt  says  she  thinks  she  could  easily  sleep  for 
twelve  hours  every  night  ;  she  is  not,  however,  sleepy  during  the  day. 

She  is  very  sensitive  to  cold  ;  during  the  winter  she  can  never,  she  says,  get 
her  hands  and  feet  warm.  The  temperature  is  usually  a  little  below  the  normal ; 
on  1 2th  September  1890,  it  was  970  Fahr. 

There  is  no  pain  or  tenderness,  even  on  firm  pressure,  over  the  vertebral 
spines  or  in  the  region  of  the  suprarenal  capsules. 

The  muscularity  is  poor  ;  the  knee-jerks  are  present,  but  very  considerably 
diminished  in  degree. 

The  pupils  are  equal,  and  moderately  dilated.  There  is  nothing  to  be  noted 
regarding  the  sensory  side  of  the  nerve  apparatus. 


ADDISON'S   DISEASE.  27 1 

The  liver  and  spleen  are  not  enlarged,  they  appear  to  be  normal  in  every 
respect.     The  lungs  are  perfectly  normal. 

Physical  examination  fails  to  detect  any  evidence  of  local  or  visceral  disease 
(other  than  the  Addison's  disease)  to  account  for  the  symptoms. 

Result. — The  patient  died  on  19th  June  1891.  She  had  been  over-fatigued 
a  few  days  previously  while  visiting  a  "  dairy  school "  ;  this  was  followed  by 
vomiting,  intense  depression,  collapse,  and  death.  Up  to  the  time  of  this  slight 
over-exertion,  she  had  continued  exceedingly  well  ;  the  discoloration  of  the 
skin  had,  her  mother  says,  faded  considerably. 

Post-mortem  examination  could  not  be  obtained. 

Case  recorded. — "Atlas  of  Clinical  Medicine,"  vol.  I.,  p.  73,  and  represented 
in  Plates  VI.  and  VII. 

CASE    11.-^- Typical  Addisoiis  Disease;  Profound  A sthenia  ;  Pigmentation  of 
the  Skin  and  Buccal  Mucous  Membrane  (the  areolce  of  the  ?tipples  not 
dark):    Very  Great  and  Rapid  Emaciation ;  No  Vomiting  Abdominal 
Pain  or  Diarrhcea  ;  History  of  a  Severe  Blow  on  the  Small  of  the  Back. 
Death :    Both    Capsules   extensively   Affected  with   the    Typical  Fibro- 
caseous  Change ;  Extensive  Deposit  of  Recent  Tubercle  in  the  Peritoneum; 
Old  Tuberculous  Lesion  at  the  Apex  of  tlie  Left  Lung. 
Male,  aged  50,  a  miner,  was  seen  as  an  out-patient  at  the  Edinburgh  Royal 
Infirmary  on  30th  June  1895,  and  was  subsequently  admitted  as  an  in-patient. 
Complaints. — Weakness  and  loss  of  flesh. 

Previous  History. — Enjoyed  good  health  till  three  years  ago.  At  that  time 
he  received  a  severe  blow  in  the  back  with  an  iron  rod — was  laid  up  in  bed  for 
a  week.  Has  gradually  "failed"  since  this  injury,  but  worked  till  three  months 
ago,  when  he  had  an  attack  of  influenza  ;  has  been  much  worse  since. 
Family  History. — Unimportant  ;  no  hereditary  tendency  to  tubercle. 
Present  Condition. — Extreme  asthenia  and  prostration  ;  expression  indicative 
of  great  lassitude  (in  going  from  the  out-patient  room  to  the  wards  he  collapsed 
and  was  found  lying  on  the  ground,  quite  conscious,  but  unable  to  get  up) ;. 
marked  emaciation — he  stated  that  he  had  lost  4  st.  during  the  past  nine 
weeks.  Heart's  impulse  imperceptible ;  heart  sounds  scarcely  to  be  heard  ; 
pulse  small,  very  soft  and  weak.  Appetite  poor,  tongue  slightly  furred  on  the 
dorsum,  red  at  the  edges  and  tip  ;  no  vomiting,  no  diarrhcea,  no  abdominal  pain 
or  tenderness.  No  rise  in  temperature.  His  medical  attendant  subsequently 
informed  me  that  there  had  been  no  abdominal  pain,  diarrhcea,  and  no  pyrexia 
throughout  the  course  of  the  illness  {i.e.,  since  the  attack  of  influenza).  Skin 
generally  dark,  especially  so  on  the  face,  neck,  back  of  the  hands,  wrists,  and 
back  (his  wife  stated  that  the  colour  of  the  skin  was  distinctly  darker  than  it  was 
before  this  illness  commenced) ;  areolae  of  the  nipples  not  darker  ;  a  distinct 
pigmented  patch  on  the  inner  side  of  the  left  cheek.  Urine  normal.  No 
evidence  of  local  disease  in  any  of  the  viscera. 

Result. — For  a  few  days  after  his  admission  to  hospital,  he  remained  in  an 
extremely  prostrate  and  semi-delirious  condition,  the  head  symptoms  being 
suggestive  of  some  form  of  intoxication.  He  refused  to  take  the  suprarenal 
extract  and  other  medicines  which  were  prescribed.  He  died  four  days  after 
admission. 

Post-mortem  examination. — Both  suprarenal  capsules  markedly  enlarged 
and  showing  the  fibro-caseous  lesion  typical  of  Addison's  disease.  Peritoneum 
studded  with  recent  grey  miliary  tubercles.     One  or  two  old  fibrous  (tubercular) 


272  DISEASES   OF   THE   BLOOD   GLANDS. 

deposits  at  the  apex  of  the  left  lung.     The  right  lung  and  the  other  organs 
healthy. 

Case  recorded. — "British  Medical  Journal,"  January  1897,  p.  1. 

CASE  III. — Case  of  Addison 's  Disease  Characterised  by  Profound  Asthenia 
and  Feebleness  of  the  Heart's  Action,  Localised  Pigmentary  Deposits  over 
One  or  Two  Vertebral  Spines  and  on  the  Buccal  JMiccous  Membrane  ; 
Great  Emaciation :  Diagnosis  Verified  on  Post-mortem  Examination  ; 
Simple  Fibrous  Atrophy  of  Both  Suprarenal  Capsules. 

Male,  aged  36,  a  seaman,  was  seen  as  an  out-patient  at  the  Edinburgh  Royal 
Infirmary  on  25th  March  1887,  and  was  subsequently  admitted  as  an  in-patient. 

Complaints. — Progressive  weakness  and  debility. 

Duration. — Six  months. 

Previous  history. — Prior  to  the  present  illness  was  a  robust  and  healthy 
man.     The  asthenia  developed  gradually  and  without  any  obvious  cause. 

Present  condition. — Extreme  prostration  ;  considerable  anaemia ;  marked 
emaciation — the  patient  stated  that  he  had  lost  3  st.  in  weight  since  his 
illness  commenced,  and  he  was  by  no  means  a  big-made  man.  Heart  sounds 
remarkably  feeble,  impulse  imperceptible,  pulse  extremely  small  and  weak. 
The  red  corpuscles  numbered  3,500,000  per  c.mm.;  they  formed  rouleaux  and 
were  normal  in  size  and  shape  ;  white  corpuscles  not  increased.  Tongue  clean, 
appetite  poor,  digestion  fairly  good,  no  vomiting,  no  diarrhoea.  No  pains  in  the 
back. 

Two  or  three  brown  discolorations  over  the  skin  of  the  dorsal  spines  ;  no 
other  discoloration  of  the  skin  ;  areolae  of  the  nipples  not  pigmented  ;  one 
small  and  quite  characteristic  pigmented  patch  on  the  buccal  mucous  membrane, 
on  the  inner  side  of  the  left  cheek,  just  opposite  the  angle  of  the  mouth. 

No  evidence  of  local  disease  in  any  of  the  viscera. 

Result. — Death  a  few  days  after  first  seen. 

Post-mortem  Examination. — The  suprarenal  capsules  were  reduced  to  small 
masses  of  fibrous  tissue.     Heart  markedly  atrophied. 

No  disease  in  any  of  the  viscera. 

Case  recorded,  "Atlas  of  Clinical  Medicine,"  Vol.  I.,  p.  54. 

CASE  IV. —  Typical  Addison's  Disease,  Characterised  by  Profoimd  and  Cause- 
less  Asthenia,   Deep    Pigmentation   of  the   Skin    and    Buccal  Mucous 
Membrane,  Pain  in  the  Back,  occasional  Vomiting  and  slight  Emaciation: 
Marked  Improvement  in  all  the  Symptoms,  including  the  Skin  Pigmen- 
tation, under  the  Administration  of  Suprarenal  Extract.     Death  from 
Influenza.     On  Post-mortem  Examination,  Absence  of  the  Capsules,  their 
place  being  taken  by  Masses  of  Fat :  in  the  position  of  the  Left  Suprarenal 
a  peculiar  Histological  Change  in  the  Fatty  Tissue,  probably  indicative 
of  the  Remains  of  the  Degenerated  Suprarenal  Capsule. 
The  patient,  a  grocer,  aged  37,  married,  was  sent  to  me  by  Dr  Mossop  of 
Bradford,  on  8th  October  1893,  suffering  from  all  the  characteristic  symptoms 
of  Addison's  disease. 

Previous  history  of  the  present  illness. — The  present  illness  commenced 
two  years  ago  ;  it  followed  a  comparatively  slight  attack  of  influenza.  After 
influenza,  he  noticed  that  his  skin  was  gradually  getting  darker.  The  discolora- 
tion is  not  worse  than  it  was  twelve  months  ago. 


ADDISON'S   DISEASE.  275, 

Previous  history  prior  to  present  illness. — Has  never  been  a  very  strong  man. 
When  22  years  of  age  he  had  to  give  up  his  original  employment,  that  of  a 
compositor,  because  of  "  weakness."  Has  not,  however,  suffered  from  any 
special  form  of  disease.  He  never  had  a  fall  or  received  any  injury  or  strain  of 
the  back  ;  has  never  been  engaged  in  hard  or  laborious  work. 

Family  history. — Unimportant ;  none  of  his  relatives  have  suffered  from 
consumption  or  scrofula.  The  patient  is  married  and  has  four  children,  all  of 
whom  are  fairly  healthy. 

Present  Condition. — Is  naturally  of  a  pale  complexion  ;  is  much  pitted  with 
small-pox,  the  result  of  a  severe  attack  thirty  years  ago.  He  complains  of 
extreme  languor  and  debility.  Is  not  appreciably  thinner.  Since  the  illness 
commenced  he  has  felt  some  pain  in  the  small  of  the  back  ;  it  has  been  worse 
during  the  past  three  months. 

The  skin  is  of  a  dark,  yellowish-brown  colour.  The  numerous  small-pox- 
pits  on  the  face  are  much  more  deeply  pigmented  than  the  other  parts  of  the 
skin  ;  in  places  they  are  almost  black.  This  appearance  was  so  peculiar  that 
I  photographed  the  patient.  There  are  numerous  small  deep-brown  moles  on 
various  parts  of  the  skin.  The  pigmentation  is  most  marked  on  the  face,  neck, 
hands  and  genital  organs,  and  it  is  over  these  parts  that  the  small  black  moles 
and  freckles  are  most  abundant.  There  are  also  numerous  pigmented  patches 
on  the  lower  lip,  and  on  several  parts  of  the  buccal  mucous  membrane. 

The  patient  complains  of  palpitation,  faintness,  and  giddiness  on  stooping. 
He  is  short  of  breath  on  exertion.  On  several  occasions  during  the  past 
three  months  he  has  vomited.  His  expression  and  bearing  are  suggestive  of 
extreme  debility.  The  heart  sounds  are  so  feeble  that  they  can  hardly  be 
heard,  and  the  cardiac  impulse  cannot  be  felt.  The  blood  is  quite  normal  ;  a 
drop  drawn  for  microscopical  examination  is  of  a  dark  purple  colour.  The  red 
blood  corpuscles  number  5,600,000  per  c.mm.,  and  the  haemoglobin  =  85  per 
cent.  There  is  no  excess  of  white  corpuscles.  No  pigment  granules  were 
detected  in  the  specimen  of  blood  which  was  examined.     The  urine  is  normal. 

Treatment. — I  advised  that  the  patient  should  be  protected  from  cold,  over- 
fatigue and  everything,  such  as  over-exertion,  likely  to  produce  exhaustion  ;. 
that  the  diet  and  condition  of  the  bowels  should  be  carefully  regulated  ;  and 
that  arsenic,  the  syrup  of  the  phosphates  and  suprarenal  extract  should  be 
administered  internally. 

Subsequent  progress  of  the  Case. — I  heard  no  more  of  the  patient  until 
20th  November  1894,  when  Dr  Mossop  sent  me  the  kidneys,  suprarenal  capsules 
and  portions  of  the  liver  and  spleen. 

Dr  Mossop  subsequently  sent  me  the  following  notes  of  the  progress  of  the 
case  from  the  time  that  I  saw  the  patient  until  his  death  : 

"Early  in  the  month  of  July  1893,  I  accidentally  met  W.  H.  G. — who  had 
been  a  patient  of  mine  in  Bradford  for  several  years  previous  to  1891 — at  a 
seaside  resort.  I  was  so  struck  with  his  appearance  that  it  occurred  to  me  that 
he  was  the  subject  of  Addison's  disease.  I  requested  him  to  call  upon  me  on  his 
return  home,  which  he  did  on  19th  July.  He  then  gave  me  the  following  history : — 

He  had  never  been  an  ailing  man,  though  not  robust,  until  two  years  pre- 
viously, when  he  had  an  attack  of  epidemic  influenza  ;  since  then  he  had  never 
fairly  recovered  his  wonted  strength  and  energy,  and  in  fact  had  gradually 
become  weaker  and  less  fit  to  follow  his  occupation — that  of  a  grocer.  When  I 
met  him  in  July  1893,  he  was  totally  unable  to  do  anything,  and  had  spent  a 
month  at  the  seaside  in  the  hope  of  recruiting  his  strength,  but  he  stated  that 


274  DISEASES   OF   THE   BLOOD   GLANDS. 

he  was  worse  than  when  he  left  home.  His  chief  complaints  were  extreme 
weakness,  loss  of  appetite,  and  sickness  on  the  least  exertion.  He  was  so 
feeble  that  he  was  only  just  able  to  dress  and  undress  himself,  and  had  to  crawl 
up  to  his  bedroom  on  his  hands  and  knees. 

His  condition  was  as  follows  : — Has  a  mournful,  emaciated  look,  as  if  he 
was  in  the  last  stage  of  phthisis,  stooping  gait  and  listless  movement,  with 
breathlessness  on  walking.  Face  and  neck  as  far  as  the  shoulders  deeply 
bronzed.  His  face  is  marked  from  small-pox  from  which  he  suffered  in  his 
youth,  the  pits  being  deeper  in  tint  than  the  rest  of  the  skin.  The  whole 
cutaneous  surface  is  discoloured,  the  backs  of  the  hands  contrasting  strongly 
with  the  whiteness  of  the  palms.  The  mucous  membrane  of  the  lips,  mouth, 
and  tongue  looks  mottled  and  blotched.  The  conjunctivae  show  unmistakably 
the  usual  pearly  whiteness.  There  are  also  a  number  of  small  darker  petechial 
spots  about  the  size  of  a  millet  seed  scattered  over  the  face  more  particularly, 
doubtless  pigmentary.  The  finger  nails  are  not  affected.  The  penis  and  scrotum 
are  also  especially  discoloured.  He  first  noticed  his  skin  darker  a  year  pre- 
viously. He  does  not  remember  having  a  fall  or  a  blow.  He  complains  .of 
vertigo,  yawning,  and  sickness,  the  latter  chiefly  in  the  morning  ;  on  stooping 
or  exertion  he  experiences  faint  feelings.  His  pulse  in  the  recumbent  position 
was  1 14,  when  standing  120;  temperature  980 ;  respirations  24.  His  bowels  are 
somewhat  constipated  ;  urine  normal.  Had  a  slight  discharge  of  blood  from 
the  anus  due  to  pile.  Tongue  clean  and  moist,  appetite  indifferent,  attacks  of 
indigestion.  Heart  sounds  normal  but  action  weak.  Lungs  healthy.  I  advised 
rest  and  nourishing  diet,  with  the  compound  syrup  of  hypophosphates. 

Three  weeks  later,  on  5th  August,  I  again  saw  him  and  found  him  a  little 
better.  Temperature  99°,  pulse  92,  respirations  20.  I  suggested  that  he  should 
see  Dr  Bramwell,  with  a  view  to  the  treatment  by  suprarenal  capsule  juice.  He 
accordingly  went  to  Edinburgh  on  7th  October  1893,  and  my  opinion  was  con- 
firmed and  a  line  of  treatment  adopted  which  I  may  say  proved  entirely  successful. 

Results  of  the  treatment. — The  patient  was  kept  in  bed  for  three  weeks,  and 
twice  a  week  I  injected  with  every  care  and  precaution  15  minims  of  the  sterilised 
suprarenal  capsule  juice  prepared  for  me  by  Messrs  Brady  &  Martin,  the 
glands  of  one  rabbit  in  :■>),  of  the  extract.  It  was  injected  alternately  over  the 
kidney  region,  and  in  a  fortnight  a  manifest  improvement  took  place  in  the 
colour  of  the  skin.  Towards  the  end  of  October,  I  tried  the  capsules  of  a  sheep 
minced  and  put  into  beef-tea.  This  brought  on  a  severe  gastric  disturbance.  I 
then  ordered  him  to  take  10-drop  doses  of  the  sterilised  juice  every  other  day  by 
the  mouth;  this  answered  admirably.  I  ordered  him  also  "Levico"  water 
(arsenio-ferrated),  for  a  time  the  mild  and  then  the  strong,  which  suited  him 
well.  His  appetite  improved,  and  a  marked  change  in  his  general  health  took 
place.  He  was  able  to  indulge  in  a  fair  amount  of  physical  exertion,  and  to 
attend  to  his  business  as  before.  His  colour  was  decidedly  better,  which  fact 
was  observed  by  other  medical  men  who  saw  him  from  time  to  time  casually. 
Ten  days  before  his  death  he  took  an  unusually  long  walk  in  the  country  (about 
eight  miles)  and  was  much  fatigued  by  it.*     At  that  time  his  wife  and  children 

*  The  fact  that  after  a  year's  treatment  with  suprarenal  extract  thepatientcould 
walk  a  distance  of  eight  miles,  whereas  before  the  treatment  was  commenced  "he 
was  so  feeble  that  he  was  only  just  able  to  dress  and  undress  himself,  and  had  to 
crawl  up  to  his  bedroom  on  his  hands  and  knees,"  speaks  volumes  in  favour  of 
the  remarkable  improvement  which  the  treatment  produced  in  this  case. 


ADDISON'S   DISEASE.  275 

were  ill  with  influenza,  his  nights  were  disturbed,  and  on  the  Friday  night  before 
his  death,  which  occurred  on  the  Sunday  morning  at  5  o'clock,  he  slept  in  the 
sitting-room  on  a  couch  before  the  fire.  He  thought  that  he  had  caught  a  chill, 
and  for  the  rest  of  the  following  day  appeared  in  a  semi-comatose  condition.  A 
medical  man  who  lived  near  at  hand  was  suddenly  sent  for ;  he  requested  my 
attendance.  At  1 1  P.M.  I  found  him  in  a  collapsed  condition,  with  pallor  of 
skin,  dilated  pupils,  and  temperature  1040,  pulse  140,  barely  conscious,  evidently 
sinking.     Restoratives  were  tried,  but  he  died  at  5  A.M.  (six  hours  afterwards)." 

Post-mortem  examination  by  Dr  Mossop. — "  The  post-mortem  was  made  on 
20th  November  1894.  In  addition  to  myself,  Ur  Walter  Nenby  and  Dr  Frith, 
House-Surgeon  to  the  Children's  Hospital,  Bradford,  were  present.  I  was  not 
allowed  to  make  a  complete  examination.  The  abdomen  and  thorax  alone  were 
examined. 

The  skin  of  the  body  had  a  bronzed  hue.  Half  an  inch  of  fat  was  present  in 
the  anterior  abdominal  wall.  The  patient  was  well  nourished,  the  muscles  being 
firm  and  of  normal  colour.  The  pericardium  and  heart  were  normal.  The  apex 
of  the  left  lung  was  adherent  by  old  pleuritic  adhesions  to  the  front  of  the  chest 
wall,  but  the  lungs  were  otherwise  normal. 

The  omentum  was  adherent  on  the  right  side  to  the  adjacent  structures. 
There  were  also  some  old  adhesions  about  the  liver  and  spleen.  The  gall 
bladder  was  distended  with  bile.  There  were  no  enlarged  glands  in  the 
abdomen.  The  spleen  was  somewhat  enlarged,  but  to  the  naked  eye  the  liver 
and  spleen  appeared  to  be  normal. 

After  removing  the  liver,  spleen,  and  stomach,  each  kidney  with  the  whole 
of  the  fatty  tissue  in  its  neighbourhood  and  (as  was  supposed)  the  suprarenal 
capsules  were  removed  en  masse.  These  parts  were  immediately  forwarded, 
together  with  portions  of  the  liver  and  spleen,  to  Dr  Bramwell  for  further 
observation."  Dr  Mossop  subsequently  wrote  saying,  "Absolutely  nothing  was 
left  in  the  body  which  could  possibly  represent  a  suprarenal  capsule." 

The  Naked-eye  Condition  of  the  Kidneys  and  Fatty  Masses  representing  the 
Suprarenal  Capsules.  —  The  tissues  received  from  Dr  Mossop  consisted  of : 
{1)  The  two  kidneys  and  large  masses  of  fat  attached  to  the  upper  end  of  each 
kidney,  in  which  it  was  supposed  the  suprarenal  capsules  were  embedded  ;  and 
(2)  portions  of  the  liver  and  spleen. 

The  masses  of  fat  which  were  supposed  to  contain  the  suprarenal  capsules 
were  first  detached  from  the  kidneys  and  carefully  examined.  They  were  of 
considerable  size,  measuring  3^  inches  by  3  inches  and  4  inches  by  3^  inches 
respectively.  An  incision  from  above  downwards  was  first  made  into  the  mass 
of  fat  corresponding  to  the  right  suprarenal  capsule,  but  no  suprarenal  capsule 
was  found.  This  mass  of  fat  was  then  cut  up  into  small  pieces,  but  the  most 
careful  examination  failed  to  detect  any  appearance  whatever  suggestive  of  a 
suprarenal  gland.  The  mass  of  fat  corresponding  to  the  left  suprarenal  capsule 
was  then  carefully  cut  into  a  series  of  transverse  sections.  In  the  centre  of  the 
fat,  a  faint,  brown,  wavy  discoloration,  which  seemed  to  correspond  exactly,  in 
respect  to  shape  and  size,  to  the  outline  of  a  normal  suprarenal  capsule,  was 
seen.  The  portions  of  fat  in  which  this  supposed  suprarenal  was  embedded  were 
immediately  placed  in  Midler's  fluid  and  handed  to  Dr  Muir,  who  kindly  under- 
took to  make  the  microscopic  examination.  The  kidney,  liver  and  spleen,  which 
were  carefully  examined  both  with  the  naked  eye  and  the  microscope,  were 
found  to  be  perfectly  normal. 

Dr   Muir's   Report  on  the  Microscopical  Examination  of  the  Mass  of  Fat 


276  DISEASES   OF   THE   BLOOD   GLANDS. 

in   which    the    Left   Suprarenal    Capsule  was    Supposed   to   be    Embedded.  — 

"  I  have  examined  three  separate  pieces  of  the  tissues,  and  all  show  similar 
appearances.  The  tissue  is  composed  of  lobules  of  fatty  tissue  with  vessels 
running  in  the  central  part.  Some  of  these  vessels  are  of  considerable  size. 
The  cells  at  the  periphery  do  not  differ  from  ordinary  fat  cells,  but  those 
arranged  around  the  vessels  show  a  peculiar  appearance.  They  are  filled  with 
small  globules  of  oil,  between  which  is  a  slightly  granular  material,  which  colours 
of  a  brown  tint  with  the  rubin-orange  stain.  These  globules  are  smaller,  and 
there  is  more  granular  material  in  the  more  centrally-placed  cells,  whilst  towards 
the  periphery  they  become  larger,  apparently  by  coalescence  and  disappearance 
of  the  granular  material.  The  appearance  is  as  if  cells  were  becoming  filled 
with  droplets  of  oil,  which  afterwards  run  together  so  as  to  produce  an  ordinary 
fat  cell — a  condition  suggesting  the  appearances  seen  in  advanced  fatty  infiltra- 
tion of  the  liver.  There  are  no  cells  which  one  can  identify  as  being  of  epithelial 
type,  and  there  is  no  arrangement  of  the  cells  in  columns,  etc.  All  the  tissue 
examined  corresponds  to  this  description.  Amongst  the  cells  undergoing  this 
change  are  a  few  leucocytes  here  and  there,  but  there  is  no  trace  of  inflammatory 
change.'  There  is  nothing,  therefore,  in  the  sections  which  would  enable  one  to 
identify  the  tissue  as  part  of  a  suprarenal.  If  it  is  so,  the  change  is  an  extreme 
fatty  infiltration,  with  ultimate  transformation  into  ordinary  adipose  tissue.  I 
am  not  familiar  with  these  appearances  as  occurring  in  ordinary  adipose  tissue. 
I  may  state  further  that  when  Dr  Bramwell  brought  to  me  the  piece  of  tissue  for 
examination,  the  brownish  sinuous  outline  in  the  fat  certainly  resembled  that  of 
a  suprarenal  ;  and  I  was  greatly  surprised  to  find,  on  microscopic  examination, 
no  trace  of  suprarenal  structure.  In  view  of  the  absence  of  anything  else  which 
could  represent  the  suprarenal,  I  agree  with  Dr  Bramwell  that  the  suprarenals 
were  entirely  absent  or  had  been  replaced  by  fat,  and  the  facts  stated  are  in 
favour  of  the  latter  view." 

Conclusion. — It  must,  I  think,  be  allowed,  either,  that  the  capsules  were 
entirely  absent,  or  that  they  were  replaced  by  fat.  The  only  other  explanation 
is  that  the  suprarenal  capsules  were  not  removed  from  the  body  and  were  not 
sent  to  me,  and  that  the  portions  of  fat  which  Dr  Muir  and  I  examined  were 
merely  portions  of  the  fat  in  which  the  kidney  is  embedded.  This  explanation 
is,  in  my  opinion,  quite  untenable.  It  is  of  course  quite  possible  in  making  a 
hurried  post-mortem  examination  to  miss  the  suprarenal  capsules.  I  have,  for 
example,  often  seen  the  right  suprarenal  capsule  removed  with  the  liver  by  an 
inexperienced  pathologist,  and  supposed  for  the  moment  to  be  absent  ;  but  in 
this  case  the  conditions  were  altogether  different.  That  the  fat  which  was 
attached  to  the  kidneys  did  actually  represent  the  remains  of  the  suprarenal 
capsules  cannot,  I  think,  be  doubted  for  the  following  reasons  : — 

1.  The  patient  had  suffered  during  life  from  symptoms  which  were  typical 
and  characteristic  of  Addison's  disease,  and  had  been  treated  for  thirteen  months 
with  suprarenal  extract  on  account  of  the  Addison's  disease.  The  case  was,  in 
fact,  regarded  as  a  typical  case  of  Addison's  disease  in  which  notable  improve- 
ment had  occurred  as  the  result  of  this  treatment. 

2.  Three  qualified  medical  practitioners  made  the  post-mortem  examination, 
with  the  express  object  of  removing  the  suprarenal  capsules.  I  am  not  acquainted 
with  two  of  these  gentlemen,  but  the  third  I  have  known  for  twenty-five  years, 
and  those  who  know  him  as  well  as  I  do  will  not  doubt  his  competence  and 
reliability. 

3.  This  gentleman  assures  me  that  everything  was   removed   which   could 


ADDISON'S   DISEASE.  277 

possibly  represent  a  suprarenal  capsule,  and  was  sent,  along  with  the  kidneys, 
immediately  to  myself.  He  states  definitely  that  nothing  was  left  in  the  body 
which  could  possibly  represent  a  suprarenal  capsule. 

4.  In  the  specimens  which  I  received  I  found  a  large  mass  of  fat  attached 
to  the  upper  end  of  each  kidney.  These  masses  of  fat  exactly  occupied  the 
position  of  the  suprarenal  capsules.  Until  I  cut  into  these  masses  of  fat  and 
examined  them  I  never  for  one  moment  doubted  that  the  suprarenal  capsules 
would  be  found  in  their  interior. 

5.  In  the  mass  of  fat  which  occupied  the  position  of  the  right  suprarenal  I 
did  not  find  anything  suggestive  of  a  suprarenal  capsule  ;  but  in  the  mass  of  fat 
which  occupied  the  position  of  the  left  suprarenal,  a  dark,  apparently  pigmented, 
sinuous  outline,  which  exactly  corresponded  in  size  and  shape  with  the  outline 
(size  and  shape)  of  a  normal  suprarenal  body,  could  be  seen  with  the  naked  eye. 

6.  Although  the  microscopical  examination  subsequently  made  by  Dr  Muir 
failed  to  show  anything  which  could  be  definitely  identified  as  the  remains  of  the 
suprarenal  capsule,  it  showed  appearances  which  are  peculiar,  and  with  which 
neither  Dr  Muir  nor  myself  are  familiar  as  occurring  in  ordinary  adipose  tissue. 
Whether  small  localised  haemorrhages  could  produce  such  appearances  or  not  1 
do  not  know. 

Now,  for  the  reasons  which  I  have  just  stated,  there  can,  I  think,  be  little  or 
no  doubt  that  the  suprarenal  bodies  were  absent,  and  that  they  were  replaced 
by  fatty  tissue.     Absence  of  the  suprarenal  capsules  has  been  noted  before.* 

From  a  practical  point  of  view,  the  marked  improvement  which  was  pro- 
duced by  the  administration  of  suprarenal  extract  is  the  most  important  point 
in  the  case.  It  raises  a  question  of  great  interest  and  practical  importance — 
namely,  Why  does  the  administration  of  suprarenal  extract  prove  beneficial  in 
some  cases  of  Addison's  disease,  whereas  in  others — and  so  far  as  our  present 
information  enables  us  to  judge  they  constitute  the  large  majority  of  cases — it 
seems  to  do  little  or  no  good  ?  As  Dr  Muir  suggested  to  me,  this  case  perhaps 
affords  an  answer  to  this  question.  In  cases  such  as  this,  in  which  the  function 
of  the  suprarenal  capsules  is  simply,  as  it  were,  suppressed,  and  in  which  there 
is  no  tubercular  lesion  and  no  involvement  of  (lesion  in)  the  abdominal  sympa- 
thetic, the  administration  of  suprarenal  extract  would  a  priori  be  expected  to 
produce  more  marked  benefit  than  in  those  cases  of  Addison's  disease  in  which 
the  lesion  of  the  capsules  is  tubercular,  and  in  which  the  abdominal  sympathetic 
is  extensively  involved.  I  may  make  my  meaning  perhaps  more  clear  by  saying 
that  if  the  thyroid  body  were  completely  destroyed  by  a  tubercular  lesion, 
symptoms  of  myxcedema  would  result ;  but  in  cases  of  complete  tubercular 
destruction  of  the  thyroid  gland  (if  such  a  condition  occurs),  the  results  of 
thyroid  treatment  would  in  all  probability  be  less  satisfactory  than  in  the 
ordinary  everyday  cases  in  which  the  tissue  of  the  thyroid  gland  is  simply 
destroyed  by  a  process  of  cirrhotic  atrophy. 

Now  in  typical  cases  of  Addison's  disease  there  is  not  only  a  tubercular 
lesion  and  abolition  of  the  function  of  the  suprarenal  capsules,  but  there  is  asso- 
ciated disease  of  the  abdominal  sympathetic.  Hence  perhaps  the  explanation 
of  the  fact  that  while  thyroid  extract  speedily  cures  myxcedema,  suprarenal 
extract  does  not  as  a  rule  produce  marked  benefit  in  cases  of  Addison's  disease. 
It  remains  to  be  seen  whether,  as  this  case  seems  to  suggest,  the  administra- 

*  By  Dr  Rispal  ("  Le  Progres  Medical,"  29th  August  1896,  and  quoted  by 
Dr  Hunter,  Glasgow,  "Medical  Journal,"  January  1897). 


278  DISEASES   OF   THE   I1LOOD   GLANDS. 

tion  of  suprarenal  extract  is  chiefly  beneficial  in  those  cases  of  Addison's  disease 
in  which  the  lesion  is  a  simple  atrophy  or  fatty  degeneration.  If  this  should 
turn  out  to  be  the  case,  we  may  in  future  be  able  to  form,  by  means  of  this 
therapeutic  test,  a  more  accurate  idea  as  to  the  exact  nature  of  the  lesion  of  the 
suprarenal  capsules  in  cases  of  Addison's  disease  than  is  possible  by  any  of  our 
present  means  of  diagnosis. 

These  therapeutic  considerations  lend,  I  think,  additional  support  to  the 
theory  which  I  have  for  long  advocated,  that  some  of  the  symptoms  of  typical 
tuberculous  cases  of  Addison's  disease  are  probably  due  to  the  tubercular  char- 
acter of  the  lesion,  and  to  the  associated  disease  in  the  abdominal  sympathetic, 
which  the  tubercular  lesion  in  the  capsules  seems  almost  invariably  to  produce, 
while  others  are  the  result  of  abolition  of  the  function  of  the  suprarenal  glands. 

Case  recorded. — "  British  Medical  Journal,"  9th  January  1897,  page  68. 

CASE  V. —  Typical  Addison's  Disease  with  Lencoderma:  Profound  Debility 
and  Languor  ;  Little  Loss  of  Flesh  ;  Pearliness  of  the  Conjunctiva  ;  Some 
Ancemia ;  Extreme  Feebleness  of  the  Heart's  Action:  Occasional  Sick 
Feeling ;  Occasional  Diarrhoea;  Tenderness  over  the  Stiprarenal  Cap- 
sules ;  Marked  and  Characteristic  Pigme7itation  of  the  Skin ;  No  Pig- 
mentation of  the  Buccal  Mucous  Membrane ;  Patches  of  Leiccodei'ma  on 
Face  and  Hands  ;  No  Obvious  Visceral  Disease.  No  Post-mortem. 
Male,  aged  41,  admitted  to  the  Newcastle-on-Tyne  Infirmary  on  1st  March 
1876. 

Complaints. — Extreme  weakness  and  pigmentation  of  the  skin. 
Duration. — Six  months. 

Previous  history. — The  debility  developed  gradually  and  without  apparent 
cause.  Patient  was  previously  healthy  ;  has  not  had  syphilis  and  has  not 
received  any  back  injury. 

Family  history. — A  sister  died  of  phthisis. 

Present  condition. — Profound  debility  and  exhaustion  ;  expression  indicative 
of  great  lassitude  ;  rather  thin,  but  little  loss  of  flesh ;  conjunctivae  pearly ;  some- 
what anaemic,  the  blood  shows  a  slight  poikilocytosis,  and  no  increase  of  the  white 
corpuscles  ;  heart's  impulse  and  sounds  extremely  feeble  ;  pulse  small,  soft  and 
weak;  frequently  feels  sick,  but  does  not  vomit  ;  occasional  attacks  of  causeless 
diarrhoea  ;  pigmentation  of  the  skin  very  marked,  especially  on  the  face,  neck, 
hands,  genitals  and  axillae  ;  areolae  of  nipples  very  dark  ;  patches  of  leucoderma 
on  the  face  and  hands  ;  no  pigmentation  of  the  buccal  mucous  membrane, 
tenderness  on  pressure  over  the  position  of  the  capsules  ;  no  visceral  disease 
detectable  in  any  of  the  organs. 

Result. — No  improvement  under  treatment ;  the  pigmentation  of  the  skin 
gradually  increased.  The  patient  remained  under  observation  for  six  months 
and  was  then  lost  sight  of.     The  ultimate  result  is  not  known. 

CASE  VI. —  Typical  Addison's  Disease :  Marked  Debility  and  Languor ;  No 
Emaciation;  Occasional  Vomiting ;  No  Diarrhoea ;  No  Back  Pain ;  No 
Anczmia ;  Very  Marked  Pigmentation  of  the  Skin ;  Numerous  Small 
Black  Moles  or  Freckles ;  Pigmentatio?i  of  the  Lower  Gum ;  Several 
Small  Ball-like  Collections  of  Pigment  in  the  Course  of  the  Liitgical 
Arteries. 
Female,  aged  8£,  seen  on  8th  October  1898. 


ADDISON'S    DISEASE.  2/9 

Complaints. — Weakness  and  lassitude  and  pigmentation  of  the  skin  ;  abso- 
lutely nothing  else. 

Duration. — Six  months. 

Previous  history. — In  May  1897,  the  patient  developed  ringworm.  A  great 
many  remedies  were  tried,  and  as  a  result  of  the  treatment  her  temper  and  health 
were  perhaps  a  little  upset ;  but,  except  that  she  did  not  play  and  romp  about  so 
much  as  usual,  nothing  special  was  noticed  wrong  with  her  until  March  1898.  It 
was  then  noticed  that  the  skin  of  her  face  was  distinctly  browner  than  formerly. 
It  was  thought  that  the  discoloration  might  perhaps  be  due  to  an  ointment  of 
creolin,  iodine,  carbolic  acid  and  sulphur  which  had  been  applied  to  the  head  a 
few  days  previously ;  the  discoloration  seemed  to  spread  from  the  hair  over  the 
face.  But  this  theory  was  soon  given  up,  for  the  discoloration  soon  extended  all 
over  the  body.  During  the  past  five  months,  the  feeling  of  lassitude  and  tiredness 
have  increased ;  and  there  have  been  occasional  attacks  of  causeless  vomiting. 
Has  never  had  a  fall  or  received  any  injury  to  her  back.  Before  this  illness 
commenced,  the  patient  was  a  particularly  strong,  active  and  lively  child. 

Family  history. — The  father,  mother,  brothers  and  sisters  are  healthy  ;  there 
are  nine  other  living  children,  all  healthy  ;  three  are  dead  (two  of  scarlet  fever 
and  one  prematurely  born)  ;  a  maternal  aunt  died  of  consumption,  and  a  cousin 
suffers  from  scrofulous  glands. 

Present  condition. — Is  a  well  developed  and  well  nourished  (fat  and  muscular) 
child  ;  she  has  not  got  any  thinner  since  the  disease  commenced.  Height  = 
4  ft.  I  in.;  weight  =  3  st.  10  lbs.  She  complains  of  nothing  except  debility  and 
muscular  weakness,  She  is  very  listless  and  depressed — a  great  contrast  to  her 
former  activity  and  liveliness.  Her  mother  says  that  if  it  were  not  for  this  list- 
lessness  and  the  discoloration  one  could  not  notice  anything  amiss  with  her. 
Appetite  good,  digestion  good,  occasional  vomiting,  no  diarrhcea.  No  pain  in 
the  back.  Conjunctivas  not  pearly,  rather  leaden-coloured.  Not  anaemic  ;  blood 
of  a  dark  purple  hue  and  perfectly  natural  on  microscopic  examination  both  of 
fresh  blood  and  stained  films  ;  no  pigmented  particles  in  the  blood.  Ringworm 
now  almost  healed  ;  scalp  not  pigmented.  The  whole  skin  is  deeply  pigmented 
of  a  brown  colour,  so  that  the  patient  resembles  one  of  the  darker  races  of  man- 
kind ;  the  face,  back  of  the  hands,  elbows,  anterior  and  posterior  folds  of  the 
axillae,  the  areolae  of  the  nipples  and  the  abdomen  are  especially  dark  ;  many 
minute  black  points,  like  pigmented  moles  or  freckles,  are  present  on  the  face, 
and  some  on  the  trunk,  forearms  and  legs.  The  gum  of  the  lower  jaw  is 
distinctly  pigmented  (of  a  golden-brown  shade),  and  several  small  accumulations 
of  pigment  are  present  under  the  tongue  along  the  course  of,  and  apparently 
adhering  to,  the  lingual  arteries.  No  pigmented  patches  on  the  tongue  or 
other  parts  of  the  buccal  mucous  membrane.  The  pigmentation  of  the  skin 
has  varied  in  depth  from  time  to  time  since  it  became  general  ;  her  mother 
thinks  it  is  now  less  deep  on  the  face  than  when  it  was  first  noticed. 

Urine  normal  in  colour  and  in  every  respect. 

Treatment. — Avoidance  of  all  fatigue,  causes  of  exhaustion  and  exposure  to 
cold  ;  careful  regulation  of  the  diet  and  bowels  ;  and  the  administration  of 
suprarenal  extract. 

Result. — Patient  has  only  been  under  observation  for  six  weeks  ;  as  yet  there 
is  no  apparent  alteration  in  the  pigmentation,  but  the  patient's  mother  is  quite 
satisfied  that  the  debility  and  languor  are  decidedly  less. 


2S0  DISEASES   OF   THE   BLOOD   GLANDS. 

CASE  VII. —  Typical  Addison! s  Disease:  Profound  Asthenia  and  Feebleness  of 
the  Hearts  Action;  Considerable  Emaciation;  Marked  Pigmentation  of 
the  Skin  and  Buccal  Mucous  Membrane;  Arcolce  oj  the  Nipples  not 
dark. 

Female,  aged  18,  seen  as  an  out-patient  at  the  Edinburgh  Royal  Infirmary 
on  25th  March  1887. 

Complaints. — Extreme  prostration  and  weakness  ;  some  headache. 

Duration. — Two  years. 

Previous  history. — Prior  to  the  onset  of  the  present  illness  was  in  good 
health  ;  the  weakness  and  emaciation  developed  gradually  without  any  obvious 
cause. 

Present  condition. — Extreme  prostration  and  weakness  ;  considerable  anaemia, 
conjunctivae  very  white  and  pearly  ;  considerable  loss  of  flesh.  Heart's  impulse 
very  weak,  heart  sounds  very  feeble,  pulse  small  and  weak.  Conjunctivae  pearly; 
patient  looks  anaemic  ;  the  red  corpuscles  (not  counted)  normal  in  size  and 
shape  ;  slight  excess  of  white  corpuscles.  Tongue  slightly  furred,  appetite  poor, 
no  vomiting,  no  diarrhoea.  Has  had  a  good  deal  of  headache  ;  it  has  not  been 
severe  until  lately.  No  pain  in  the  back  until  to-day.  Complexion  naturally 
dark,  but  the  skin  has  become  very  much  darker  since  the  illness  com- 
menced ;  the  skin  generally  is  of  a  dirty  brown  colour  and  is  especially  dark 
over  the  abdomen  ;  the  breasts  are  very  small  ;  the  areolae  of  the  nipples  are 
not  pigmented  ;  there  are  numerous  pigmented  patches  on  the  buccal  mucous 
membrane  and  on  the  lower  lip  at  the  junction  of  the  skin  with  the  mucous 
membrane. 

No  evidence  of  local  disease  in  any  of  the  viscera,  except  the  suprarenal 
capsules. 

Result. — Not  known. 


CASE  VIII. —  Typical  Addison's  Disease :  Profound  Prostration  ;  Feebleness  of 
the  HearVs  Action  ;  Occasional  Vomiting;  Frequent  Pains  in  the  Back ; 
Pigmentation  of  the  Skin  ;  Areolce  of  the  Nipples  not  dark ;  One  Pig- 
mented Patch  on  the  Buccal  Mucous  Membrane. 

Male,  aged  46,  factory  worker,  seen  as  an  out-patient  at  the  Edinburgh 
Royal  Infirmary  on  23rd  June  1889. 

Complaints. — Great  weakness. 

Duration. — Four  months. 

Previous  history. — Enjoyed  good  health  until  the  present  illness  commenced  ; 
the  weakness  developed  gradually  and  without  any  obvious  cause. 

Present  condition. — Extreme  prostration  and  weakness;  considerable  anaemia; 
no  loss  of  flesh.  Heart's  impulse  weak,  first  sound  short  and  sharp  ;  pulse  small 
and  weak.  Patient  looks  somewhat  anaemic  ;  conjunctivae  pearly  ;  the  red  cor- 
puscles (not  counted)  for  the  most  part  normal  in  size  and  shape,  a  few  tailed 
(slight  poikilocytosis),  no  excess  of  whites.  Tongue  clean,  appetite  poor,  occa- 
sional vomiting,  no  diarrhoea.  Frequent  pain  in  the  small  of  the  back.  Skin 
generally  much  darker  ;  the  areolae  of  the  nipples  not  darker  ;  well  marked 
pigmented  patch  on  the  buccal  mucous  membrane.  Urine  contains  a  trace  of 
albumen  and  becomes  very  dark  on  the  addition  of  nitric  acid.  No  evidence  of 
local  disease  in  any  of  the  viscera. 

Result. — Not  known. 


ADDISON'S   DISEASE.  28l 

CASE  IX. — Addisoiis  Disease,  Complicated with  Enlargement  of  the  Lymphatic 
Glands,  Liver  a?id  Spleen  {?  Hodgki?is  Disease  or  Tubercle)  a?id  Derma- 
titis Herpetiformis :  No  Post-mortem. 
Female,  aged  19,  admitted  to  the  Edinburgh  Royal  Infirmary  on  18th  August 

1893. 

Complaints. — Great  weakness,  emaciation,  pigmentation  of  the  skin,  itching, 
sweating  and  cough. 

Duration. — One  year. 

Previous  history. — Two  years  ago  the  patient  began  to  suffer  from  itching  of 
the  skin  ;  it  commenced  on  the  heels  and  soles  ;  little  vesicles  developed  from 
time  to  time  ;  the  eruption  and  itching  gradually  extended,  involving  the  legs, 
thighs,  arms,  and  finally  the  trunk,  head,  face  and  neck.  Small  red  papules 
which  were  very  itchy  appeared  from  time  to  time  on  the  legs  and  arms,  but 
never  on  the  face  or  trunk.  It  was  a  year  before  the  itching  extended  over  the 
whole  body. 

Soon  after  the  itching  commenced,  she  began  to  sweat  profusely,  first  on  the 
face  and  then  all  over  the  body.  She  also  noticed  that  her  skin  was  becoming 
darker,  and  that  her  hair,  which  was  previously  very  luxuriant,  was  coming  out ; 
at  the  same  time  her  hair  got  lighter  in  colour  and  drier  in  texture.  The  loss  of 
hair  was  not  confined  to  the  head  but  affected  the  eyebrows,  axillae,  and  pubes. 

In  August  1892,  she  had  an  attack  of  influenza  and  since  then  has  gradually 
got  weaker  and  thinner  ;  for  the  past  year  she  has  been  almost  confined  to  bed. 

In  December  1892,  some  enlarged  glands  were  noticed  in  the  axillae.  About 
a  year  ago,  the  menstruation  stopped.  For  the  past  three  months,  she  has  had 
a  cough,  but  little  or  no  expectoration. 

Family  history. — She  inherits  a  strong  rheumatic  tendency ;  one  brother  had 
scrofulous  glands  in  the  neck.  No  other  relations,  so  far  as  she  knows,  have 
been  tubercular. 

Present  condition. — Extreme  prostration  and  weakness  and  appearance  of 
profound  lassitude;  marked  emaciation — height  =  5  ft.  \\  ins.;  weight  =  5  st. 
12  lbs.  Temperature  continuously  above  the  normal  (morning  temperature 
about  990,  evening  temperature  about  101.50).  Pulse  quick,  small  and  weak 
(78  to  130).  Appetite  very  good,  no  dyspepsia,  no  vomiting,  no  diarrhoea. 
Occasional  pain  in  the  back. 

Heart's  impulse  not  perceptible  ;  heart  sounds  very  feeble.  Red  corpuscles 
number  3,980,000,  normal  in  size  and  shape  ;  haemoglobin  =  62  per  cent.;  slight 
excess  of  white  corpuscles. 

Skin  thin,  but  dry  and  harsh;  very  deeply  pigmented,  of  a  dirty  brown 
colour  like  that  of  some  of  the  darker  races ;  many  minute  black  points  (freckles); 
some  larger  white  spots  about  the  size  of  a  very  small  pea,  apparently  the  result 
of  former  vesicles  or  scratchings  ;  no  papules  or  vesicles  ;  areolae  of  nipples  very 
deeply  pigmented ;  no  pigmented  patches  on  the  buccal  mucous  membrane. 
Head  almost  bald,  and  hair  of  eyebrows,  axillae  and  pubes  very  scanty. 

The  patient  complains  of  great  itchiness  of  the  skin. 

Enlarged  glands  on  both  sides  of  the  neck,  and  in  both  axillae  ;  an  enlarged 
gland  in  the  second  right  intercostal  space.  The  enlarged  glands  are  hard  and 
painless. 

A  solid  mass,  apparently  enlarged  glands,  in  the  upper  part  of  the  right 
thoracic  cavity  (marked  dulness  and  resistance  on  percussion  from  the  right 
clavicle  to  the  3rd  rib  in  front  and  in  the  supraspinous  and  right  axillary 
regions) ;  no  moist  sounds  ;  over  the  dull  area  the  breathing  was  in  places 


282  DISEASES   OF   THE   BLOOD   GLANDS. 

bronchial  and  the  vocal  resonance  and  fremitus  increased.  Some  cough  and 
shortness  of  breath  when  lying  on  the  back  ;  very  scanty  frothy  expectoration  ; 
no  tubercle  bacilli.     No  evidence  of  phthisis. 

Liver  somewhat  and  spleen  considerably  enlarged. 

Urine  normal,  except  that  it  gave  Ehrlich's  reaction  on  several  occasions. 

Diagnosis. — The  case  seemed  to  be  one  of  Addison's  disease,  with  Hodgkin's 
disease  or  solid  tubercular  enlargement  of  the  glands,  and  dermatitis  herpeti- 
formis. 

Treatment. — A  great  number  of  remedies  (cod-liver  oil,  quinine,  iron,  car- 
bonate of  guaiacol,  strychnine,  arsenic,  thyroid  extract,  atropin,  sulphate  of 
atropia,  morphia,  bromide  of  potassium,  together  with  menthol  and  other  local 
remedies)  were  employed,  but  with  no  benefit. 

Result. — The  patient  remained  in  hospital  until  28th  December  1893  (five 
months)  ;  there  was  no  improvement  ;  during  the  whole  of  her  stay  in  hospital, 
the  temperature  was  above  the  normal  (990  to  1020)  :  she  became  thinner,  weaker 
and  more  anaemic  ;  on  15th  November  the  red  corpuscles  numbered  1,179,000 
and  the  haemoglobin  =  38  per  cent.;  the  skin  became  darker.  She  was,  contrary 
to  advice,  taken  home  by  her  friends,  and  died,  in  Orkney,  on  10th  January 
1894.  The  true  nature  of  the  case  was  consequently  not  verified  by  post-mortem 
examination. 

CASE  X. — Suspected  Addison's  Disease  ;  Extreme  Debility  without  Obvious 
Cause  ;  Feebleness  of  the  Heart's  Action ;  Pain  in  the  Back ;  Marked 
Pigmentation  of  the  Skin  ;  Pearliness  of  the  Cofiju?ictivcE  ;  No  Ancemia  ; 
No  Obvious  Visceral  Disease. 

Male,  aged  49,  seen  on  14th  August  1895. 

Complaints. — Great  weakness. 

Duration. — Eighteen  months. 

Previous  history. — The  debility  commenced  eighteen  months  ago  without 
obvious  cause  ;  some  anaemia  developed,  but  disappeared  under  arsenic  and  iron. 

Family  history. — Unimportant. 

Present  condition. — Extreme  debility  ;  very  slight  loss  of  weight  ;  no  vomit- 
ing ;  no  diarrhoea  ;  some  pain  in  the  back  over  the  region  of  the  capsules  ; 
conjunctivae  very  pale  and  pearly,  but  lips  not  anaemic  ;  heart's  impulse  and 
sounds  feeble  ;  pulse  weak  ;  sleeps  too  much  ;  skin  of  face,  hands,  thighs  and 
genitals  very  dark — much  more  so  than  they  used  to  be  ;  areolae  of  nipples 
somewhat  dark ;  no  pigmented  patches  in  the  mouth  ;  no  visceral  disease 
detectable  in  any  of  the  organs  ;  knee-jerks  exaggerated  ;  gait  rather  unsteady. 

Diagnosis. — Difficult,  but  condition  suggestive  of  Addison's  disease. 

Result. — Not  known. 

CASE    XI.  —  Suspected  Addison's   Disease   {Extreme  Asthe?iia,   Emaciation, 
Paroxysmal  Attacks  of  Gastric  Pain   ajtd   Vomiting  without   Obvious 
Stomach  Cause,  Pain  in  the  Back  and  Tenderness  on  Pressure  over  the 
Suprarenal  Capsules,  Pigmentation  of  the  Skin  and  Palate):  Recovery. 
Female,  aged  25,  was  seen  in  October  1885. 

Complaints. — Extreme  debility,  emaciation,  pain  in  the  back,   paroxysmal 
attacks  of  gastric  pain  and  vomiting. 
Duration. — Three  and  a  half  years. 

Previous  history.  —  Six  or  seven  years  ago,  patient  had  two  attacks  of 
bronchitis.     Three  and  a  half  years  ago,  she  suffered  from  severe  gastric  pain, 


ADDISON'S   DISEASE.  283 

going  through  to  the  back,  with  persistent  vomiting  for  a  day  or  two.  There 
have  been  two  similar  attacks  since  ;  the  last  occurred  four  months  ago,  and 
was  followed,  for  several  weeks,  by  pain  after  food  and  extreme  irritability  of  the 
stomach  ;  this  attack  was  attended  with  marked  collapse.  For  the  past  year, 
she  has  suffered  from  pain  in  the  lower  dorsal  region  increased  by  exertion. 

Family  history. — Good  ;  her  father  died  of  pneumonia  at  the  age  of  56. 

Present  condition. — Extreme  debility  and  lassitude ;  considerable  emaciation; 
heart's  action  feeble  ;  pulse  small  and  weak  ;  temperature  subnormal  ;  some- 
what anaemic ;  tongue  clean,  appetite  poor,  no  pain  or  tenderness  in  the  epigastric 
region  ;  the  attacks  of  gastric  pain  and  vomiting  occur,  sometimes  at  all  events, 
without  any  obvious  gastric  cause  ;  one,  which  I  had  the  opportunity  of  seeing, 
appeared  to  be  clue  to  over-exertion  ;  it  resembled  one  of  the  gastric  crises  of 
locomotor  ataxia  ;  no  diarrhoea.  There  is  distinct  tenderness  on  pressure  in 
each  lumbar  region  (i.e.,  over  the  suprarenal  capsules).  No  spinal  caries. 
Several  pigmented  patches  on  the  skin  of  the  arms,  thighs  and  over  the  dorsal 
vertebrae  ;  one  pigmented  patch  on  the  soft  palate.  Skin  somewhat  dry  and 
rough.  Menstruation  profuse  and  attended  with  a  good  deal  of  pain.  No 
evidence  of  disease  in  any  of  the  viscera. 

Diagnosis.— Difficult ;  it  lay  between  gastric  ulcer  and  Addison's  disease. 
The  marked  emaciation,  the  rough  and  dry  condition  of  the  skin,  and  the  fact 
that  the  patient  has  recovered  are  against  Addison's  disease  ;  but  the  other 
symptoms,  more  especially  the  pigmented  patch  on  the  palate,  were  in  favour  of 
that  condition.  When  the  patient  was  under  my  observation  I  was  of  opinion 
that  she  was  suffering  from  Addison's  disease. 

Result.— Under  cod-liver  oil,  maltine,  arsenic,  the  local  application  of  iodine 
over  the  region  of  the  suprarenal  capsules  and  residence  in  a  warm  climate,  the 
patient  slowly  but  gradually  improved.  Though  not  robust,  she  is  now  (October 
1898)  in  the  enjoyment  of  fair  health. 

CASE  XII.— Pigmentation  of  the  Skin,  Exactly  Resembling  that  of  Addison's 
Disease,  with  Caseous  Destruction  of  One  Suprarenal  Capsule,  the  other 
being  healthy. 

In  this  very  interesting  but  complicated  case,  the  skin  was  deeply  pigmented, 
exactly  as  it  is  in  advanced  Addison's  disease,  and  after  death  the  left  supra- 
renal capsule  was  found  to  be  twice  the  natural  size  and  transformed  into  a  putty- 
like mass,  the  right  suprarenal  capsule  being  normal. 

The  patient  suffered  from  an  intrathoracic  tumour  which  closely  simulated 
an  aneurism.  During  the  course  of  his  illness  right-sided  hemiplegia  and 
aphasia  developed  ;  also  pericarditis. 

On  post-mortem  examination,  the  following  conditions,  in  addition  to  the 
lesion  of  the  left  suprarenal  capsule,  were  found  :— Recent  pericarditis  ;  a 
sacculated  dilatation  of  the  upper  part  of  the  pericardium  ;  a  tumour  involving 
the  root  of  the  left  lung  ;  a  large  cyst  in  the  left  frontal  lobe  ;  a  recent  embolism 
in  left  middle  cerebral  artery. 

The  notes  are  as  follows  : — 

W.  A.,  a  pitman,  aged  45,  was  admitted  to  the  Newcastle  Infirmary  on  1st 
October  1874,  suffering  from  right-sided  hemiplegia,  cough,  emaciation,  and 
debility. 

Previous  history. — At  the  age  of  22,  he  had  an  attack  of  "  inflammation  of  the 
chest."  With  this  exception,  he  enjoyed  excellent  health  until  November  1873, 
when  he  caught  cold.     His  eyes  and  nose  began  to  run,  and  continued  to  do  so 


284  DISEASES   OF   THE    BLOOD   GLANDS. 

for  some  time,  hi  April  1874,  he  began  to  cough  and  lose  flesh.  In  August, 
he  commenced  to  spit  ;  the  sputa  were  white  and  frothy,  never  blood-tinged. 
He  rapidly  lost  flesh  ;  complained  occasionally  of  pain  in  the  chest  and  of 
palpitation.  He  never  seemed  very  short  of  breath.  Six  weeks  before  admission 
to  hospital,  a  marked  change  took  place  in  his  mental  condition  ;  he  became 
very  irritable  and  obstinate  ;  slept  badly  ;  would  sit  silent  for  hours  together  ; 
when  spoken  to,  he  answered  in  monosyllables.  A  week  before  admission,  he 
partly  lost  the  use  of  his  right  hand.  A  few  days  afterwards,  the  leg  became 
affected.  He  was  at  work,  off  and  on,  as  a  pitman,  until  a  fortnight  before 
admission  to  hospital. 

Family  history. — Good  ;  none  of  his  near  relatives  have  died  of  cancer  or 
consumption. 

Condition  on  admission. — The  skin  was  of  a  dirty  brown  colour.  His  wife 
said  it  was  much  darker  than  it  used  to  be.  There  were  no  pigmented  patches 
on  the  buccal  mucous  membrane.  He  was  very  thin  and  emaciated.  He  was 
unable  to  give  any  account  of  himself  or  of  his  complaints.  He  said  "Yes," 
"  n0;"  «  Nicely,"  or  some  short  word,  in  answer  to  all  questions.  He  seemed  to 
understand  fairly  well  what  was  said  to  him.  There  was  partial  loss  of  power  in 
the  right  arm  and  leg.  Sensibility  was  apparently  natural.  The  muscles  of  the 
right  hand  and  arm  were  not  more  wasted  than  those  of  the  body  generally. 
Muscular  irritability  was  very  marked.  His  sight  seemed  good.  The  pupils 
were  equal  and  contracted.  (At  this  time,  I  was  not  in  the  habit  of  using  the 
ophthalmoscope  in  all  cases,  for  I  had  not  then  realised  the  truth  of  Dr  Hugh- 
lings  Jackson's  observation  that  optic  neuritis  is  often  present  with  perfect  vision. 
I  regret,  therefore,  that  I  cannot  state  what  was  the  condition  of  the  optic  discs.) 
The  other  special  senses  seemed  natural.  The  tongue  was  protruded  in  the 
middle  line.  He  was  very  irritable  and  obstinate,  slept  badly,  and  often  ground 
his  teeth.  The  anterior  wall  of  the  left  chest  was  unduly  prominent  from  the 
second  to  the  sixth  rib.  It  measured,  at  the  level  of  the  nipple,  half  an  inch 
more  than  the  right,  being  eighteen  inches.  Pulsation  could  be  seen  and  felt 
over  the  prominent  area.  The  pulsation  seemed  to  come  to  a  focus  at  a  spot  an 
inch  and  a  half  above  and  slightly  outside  the  left  nipple.  It  was  apparently 
distinct  from  the  cardiac  pulsation  and  quite  as  forcible.  On  percussion,  there 
was  absolute  dulness  over  the  left  chest — anteriorly,  from  the  clavicle  to  the 
sixth  rib  ;  laterally,  in  the  axillary  region  ;  posteriorly,  in  the  suprascapular, 
upper  half  of  the  scapular,  and  upper  half  of  the  interscapular  region  on  the  left 
side.  Pain  was  complained  of  on  percussion  about  the  left  nipple.  On  the 
right  side,  there  was  dulness  over  an  area  an  inch  square  below  the  sterno- 
clavicular articulation.  This  dulness  was  directly  continuous  on  its  inner  side 
with  the  dulness  on  the  left  side.  The  cardiac  dulness  could  not  be  exactly 
defined  by  percussion,  owing  to  the  surrounding  dulness.  The  apex-beat  could 
be  seen  and  felt  between  the  fifth  and  sixth  ribs  an  inch  and  a  half  below  the 
nipple.  On  auscultation,  the  respiratory  murmur  was  scarcely  perceptible  over 
any  part  of  the  left  chest ;  it  was  entirely  absent  from  the  second  to  the  sixth 
ribs  anteriorly.  Over  the  rest  of  the  dull  area,  faint  bronchial  breathing  was 
heard.  Vocal  resonance  was  greatly  diminished  all  over  the  left  chest  ;  absent 
over  the  dull  area.  At  the  aortic  cartilage,  the  first  sound  was  replaced  by  a 
soft  bellows-murmur.  The  second  sound  was  well  marked.  Over  the  pulmonary 
area,  the  systolic  murmur  was  heard,  being  fainter  than  over  the  aorta.  The 
second  sound  was  louder  than  the  aortic.  At  the  apex,  the  sounds  had  a  dull 
thudding  character.    At  the  point  of  pulsation,  an  inch  and  a  half  above  the  left 


ADDISON'S   DISEASE.  285 

nipple,  both  cardiac  sounds  were  very  distinct,  but  free  from  murmur.  The  radial 
pulse  numbered  92,  was  weak,  regular,  equal  in  the  two  wrists.  The  respirations 
numbered  20.  The  temperature  was  normal.  There  was  no  excess  of  the  white 
blood-corpuscles.  The  red  corpuscles  did  not  form  rouleaux,  but  adhered 
wherever  they  came  into  contact.  The  urine  contained  an  excess  of  phosphates. 
The  other  organs  were  normal. 

The  subsequent  progress  of  the  case  was  as  follows  : — 

ijth  October. — His  mental  condition  was  much  worse.  The  paralysis  of  the 
arm  and  leg  was  now  complete.  There  was  also  distinct  loss  of  power  in  the 
muscles  of  the  right  side  of  the  face.  The  heart  was  situated  more  to  the  left 
side.  The  apex  was  now  an  inch  outside  the  left  nipple.  The  dulness  over  the 
upper  half  of  the  left  lung  was  more  absolute  and  extensive. 

19//?  October. — A  well-marked  pericardial  friction-murmur  was  heard  over 
the  greater  part  of  the  left  chest  anteriorly  ;  it  was  very  abruptly  defined.  The 
cardiac  sounds  were  heard,  free  from  murmur,  in  the  axillary  region. 

2\st  October. — The  left  chest  now  measured  an  inch  and  a  half  more  than 
the  right. 

28th  October. — He  was  very  much  better,  and  was  gaining  power  in  the  right 
arm  and  leg.     The  friction-sound  was  now  almost  gone. 

4th  November. — He  could  move  the  arm  and  leg  freely. 

$th  November. — He  had  again  lost  all  power  in  the  right  arm  and  leg.  His 
face  was  very  much  congested  ;  breathing  very  difficult.  He  had  been  several 
times  severely  purged  without  medicine. 

6th  November. — He  was  again  severely  purged.     He  died  at  9.30  P.M. 

Temperature. — The  temperature  never  exceeded  100  deg.  Fahr.  until  5th 
November ;  on  that  day,  it  reached  101  deg.  ;  and  on  6th  November,  102  deg. 

Post-mortem  examination,  made  eighteen  hours  after  death. — Body  much 
emaciated ;  rigor  mortis  well  marked ;  the  left  pupil  dilated,  the  right 
contracted. 

Both  lungs  were  firmly  adherent  throughout.  The  left  was  scarcely  visible 
on  opening  the  chest,  its  anterior  edge  being  much  retracted.  Between  the 
sternum  and  adjacent  parts,  there  was  a  quantity  of  recent  lymph.  The  fleri- 
cardium  was  adherent  over  the  greater  part  of  the  heart.  Along  the  right 
border  and  at  the  apex,  it  was  free.  The  adhesions  were  recent  and  thick. 
Around  the  great  vessels,  the  pericardium  was  dilated,  and  formed  a  sort  of 
cyst,  which  projected  to  the  left  side.  The  sac  was  about  the  size  of  an  orange, 
and  was  filled  with  pinkish  semi-fluid  matter.  The  heart  weighed  twelve 
ounces.  Its  valves  were  healthy.  The  outer  coat  of  the  aorta  and  pulmonary 
artery,  where  surrounded  by  the  cyst,  were  roughened  and  coated  with  lymph. 

Aroicnd  the  root  of  the  left  lung,  and  extending  into  the  substance  of  the 
organ,  was  a  growth  of  brain-like  consistency,  and  composed  of  numerous 
nodules.  The  growth  radiated  into  the  lung-substance  in  all  directions,  and 
seemed  to  follow  the  course  of  the  bronchi,  the  walls  of  which  were  much 
thickened.  The  terminal  portions  of  the  aortic  arch  and  pulmonary  artery 
were  surrounded  by  the  growth,  which  passed  over  to  the  right  side.  On  section, 
the  nodules  were  of  a  pink  colour;  one  was  caseous.  The  left  lung  was  of  a 
jet-black  colour.  The  black  fluid  which  escaped  did  not  stain  the  fingers. 
After  the  black  fluid  had  been  washed  out,  the  lung-substance  was  tough  and 
non-crepitant,  resembling  the  compressed  lung  from  a  case  of  copious  pleuritic 
effusion.  The  right  lung  was  congested,  otherwise  healthy.  There  were  no 
tubercles. 


286  DISEASES   OF    THE   BLOOD   GLANDS. 

The  mesenteric  glands  were  much  enlarged,  of  a  dark  purple  colour,  and 
studded  here  and  there  with  white  nodules.  A  chain  of  enlarged  glands  sur- 
rounded the  abdominal  aorta.  In  the  lower  part  of  the  ileum,  there  was  an 
oval  nodule  of  fully  the  size  of  a  large  walnut;  it  formed  a  well-defined  tumour; 
its  free  surface  was  of  a  yellow  colour,  evidently  stained  by  feces.  Several 
Peyer's  patches  were  enlarged,  but  none  were  ulcerated. 

The  left  suprarenal  capsule  was  about  twice  the  natural  size  and  transformed 
into  a  cheesy  putty-like  mass.     The  right  suprarenal  capsule  was  normal. 

The  surface  of  the  brain  was  considerably  congested.  An  abscess  of  the 
size  of  an  egg  was  situated  in  the  middle  of  the  left  frontal  lobe.  The  white 
matter  was  extensively  destroyed.  At  one  point  corresponding  to  the  middle 
of  the  superior  frontal  convolution,  the  grey  matter  was  invaded  and  partly 
destroyed.  The  abscess  contained  a  grumous  yellow  liquid  of  the  consistency 
of  thin  cream;  it  was  lined  by  a  ragged  membrane.  Both  lateral  ventricles 
contained  an  excess  of  fluid.  A  clot  was  found  in  the  left  middle  cerebral 
artery  just  at  its  commencement. 

On  microscopic  examination^  the  intrathoracic  growth  was  found  to  consist 
of :— i.  Cells,  round  and  angular  in  form,  about  the  size  of  white  blood-cor- 
puscles, and  containing  numerous  highly  refractive  granules;  2.  Free  nuclei 
and  granules;  3.  Fibrous  tissue;  many  of  the  fibres  were  nucleated.  The 
pericardium,  the  cerebral  abscess,  and  the  lymphatic  glands,  contained  the 
same  corpusclar  elements  as  the  tumour. 

Remarks. — It  may,  perhaps,  be  objected,  that  the  discoloration  of  the  skin 
was  due  to  some  other  cause  than  the  lesion  of  the  left  suprarenal  capsule;  in 
short,  that  it  was  not  the  bronzing  of  Addison's  disease.  But  I  see  no  reason 
to  adopt  this  view ;  for  the  condition  of  the  capsule  was  exactly  similar  to  that 
which  so  frequently  results  from  the  "peculiar  quasi-tubercular  change  which 
produces  the  symptoms  of  Addison's  disease."  It  is  an  unfortunate  fact  that 
there  is  not  in  my  case-book  a  more  minute  description  of  the  discoloration, 
and  I  cannot  at  this  distant  period  trust  my  memory  to  fill  in  details.  I  cannot, 
for  instance,  say  whether  the  discoloration  was  more  marked  in  the  axillae  and 
genitals  than  elsewhere.  There  certainly  were  no  pigmented  patches  on  the 
buccal  mucous  membrane. 

I  do  not  make  any  mention  of  the  constitutional  symptoms,  the  anaemia, 
etc.,  which  are  characteristic  of  Addison's  disease,  the  case  being  so  very  com- 
plicated. The  emaciation  is  fully  accounted  for  by  the  complications  which 
were  present.  It  is  unnecessary  for  my  present  purpose  to  refer  to  the  many 
other  interesting  features  of  the  case ;  they  are  considered  in  the  original 
record  of  the  case. 

Recorded  in  the  "  British  Medical  Journal,"  3rd  March  1877,  p.  256. 


MYXCEDEMA. 

Definition. — The  term  myxoedema  in  reality  represents  a  group 
of  clinical  symptoms  and  pathological  changes  which  may  result 
from  any  condition  which  causes  arrested  development  of  the 
thyroid  gland  or  which  produces  abolition  of  the  function  of  the 
thyroid  gland.  But  since,  in  the  vast  majority  of  cases  of  idio- 
pathically  developed  myxoedema  in  man,  the  myxcedematous 
state  is  the  result  of  one  particular  morbid  process  in  the  thyroid 
gland,  viz.,  cirrhotic  atrophy,  the  term  myxoedema  (like  epilepsy) 
may  be  retained  and  applied  in  particular  to  this,  the  usual,  form 
of  the  condition. 

Historical  Note. — The  clinical  features  of  this  remarkable 
disease  were  first  described  by  the  late  Sir  William  Gull,  in  the 
year  1873,  in  a  paper  read  before  the  Clinical  Society  of  London, 
entitled  "A  cretinoid  state  supervening  in  adult  life  in  women." 
In  the  year  1878,  Dr  Ord  published  an  important  paper  on  the 
subject  and  discussed  the  pathology  of  the  disease.  In  consequence 
of  the  large  quantity  of  mucin  which  was  found  in  the  subcutaneous 
tissues  of  one  of  his  cases  he  proposed  the  name  "  myxoedema," 
which  the  disease  now  bears  ;  and  although  subsequent  analyses 
have  for  the  most  part  failed  to  confirm  Dr  Ord's  observations  on 
this  point,  the  name  myxoedema  has  been  retained.  In  the  year 
1888,  the  Clinical  Society  of  London  issued  a  very  valuable  report 
upon  the  subject.  During  the  past  seven  years,  in  consequence  of 
the  great  attention  which  has  been  directed  to  the  subject  since  the 
introduction  of  the  thyroid  plan  of  treatment,  our  knowledge  of  the 
disease  has  been  rendered  very  complete  by  the  observations  of 
many  different  physicians.  The  literature  of  the  disease  is  now 
most  extensive. 

It  is  remarkable  that  the  first  account  of  myxoedema  was  only 
published  some  twenty-five  years  ago  ;  for,  in  this  country  at  all 
events,  the  disease  is  comparatively  common,  its  clinical  features  are 
very  striking,  and,  when  the  disease  is  fully  developed,  different 
cases  present  an  extraordinary  resemblance  one  to  another. 

It  can  hardly  be  doubted  that  the  clinical  features  of  myxoedema 


288  DISEASES   OF   THE    BLOOD   GLANDS. 

must  have  been  regarded  as  peculiar  by  many  observers  before  the 
first  written  description  was  published  by  Sir  William  Gull  in  the 
year  1874 ;  and  that  other  physicians  must  have  come  to  the  same 
conclusion  that  Gull  did,  viz.,  that  the  condition  was  a  definite  and 
distinct  disease.  I  know  that  this  was  so  in  one  instance  at  any 
rate,  for  in  the  year  1869,  when  I  joined  my  father  in  practice,  he 
showed  me  a  splendid  example  of  the  disease  and  demonstrated  to 
me  in  that  patient  many  of  the  clinical  features  which  are  now 
known  to  be  most  important  and  characteristic,  viz. : — The  peculiar 
(solid)  character  of  the  oedema  ;  the  normal  condition  of  the  urine ; 
the  pink  blush  on  the  cheeks  ;  the  translucent,  ivory-like  appear- 
ance of  the  skin  of  the  face  and  eyelids  ;  the  dulness  of  the 
intellect ;  the  remarkable  slowness  of  thought  and  speech ;  the 
debility  and  lassitude  for  which  there  was  no  obvious  cause ;  the 
persistent  low  temperature,  and  the  extreme  susceptibility  to  cold, 
which  most  myxoedematous  patients  complain  of.  He  told  me 
that  he  believed  the  condition  was  a  new  disease — a  disease  which 
had  never  been  described. 

Since  the  disease  was  recognised  as  a  distinct  clinical  entity 
many  physicians  have  been  able  to  recall  typical  cases  which  were 
previously  under  their  observation,  and  which  they  had  regarded  as 
peculiar  without  knowing  exactly  what  they  were.  Thus,  Dr 
Ireland,  of  Prestonpans,  tells  me  that  in  the  year  1854,  he  attended 
a  lady  in  Edinburgh,  who  was  suffering  from  a  peculiar  form  of 
dropsy  which  did  not  conform  to  any  of  the  then  recognised  types  ; 
and  that  on  looking  back  to  that  case  (which  proved  fatal  a  year 
after  he  first  saw  it)  he  distinctly  remembers  that  it  presented  all 
the  characteristic  peculiarities  of  myxcedema.  Another  medical 
friend  wrote  me  as  follows  (and  I  have  had  several  other  com- 
munications to  the  same  effect) : — 

"  I  have  been  reading  the  description  of  myxcedema  in  your  '  Atlas  of 
Clinical  Medicine'  with  great  interest  and  am  much  instructed  thereby.  My 
reason  for  troubling  you  with  this  letter  is,  that  I  have  had  good  reason  for 
knowing  the  symptoms  well,  as  my  dear  old  mother  without  doubt  died  from  the 
disease  as  far  back  as  1 871— two  or  three  years  before  the  disease  was  properly 
described.  It  used,  I  remember,  to  worry  me  greatly  that  Warburton  Begbie 
and  Sir  R.  Christison  were  unable  to  give  any  satisfactory  explanation  of  her 
great  feebleness,  especially  as  she  had,  as  they  said,  no  organic  disease. 
Begbie  was  always  giving  her  iron  as  he  said  she  was  anaemic.  The  legs  were 
cedematous,  but  the  urine,  which  I  frequently  tested,  was  always  free  from 
albumen.  I  enclose  a  photo  taken  about  six  months  before  her  death.  You 
will  notice  the  marked  double  ptosis  and  the  elevation  of  the  eyebrows.  She 
had  most  of  the  characteristic  symptoms  you  mention — unaccountable  feeble- 
ness, constant  subjective  sensation  of  cold,  slow  speech,  and  gait.  A  hot  sea- 
water  bath  used  to  brighten  her  up  more  than  anything  else.     The  immediate 


MYXCEDEMA.  289 

cause  of  death  was  obstruction  of  the  bowels.  She  had  been  fifteen  years  in 
India,  but  had  eight  or  nine  years  of  good  health  after  her  return  to  this 
country  ;  then,  about  eleven  years  before  her  death,  the  disease  (myxcedema) 
developed." 

Etiology. 

Locality. — Myxoedema  is,  comparatively  speaking,  a  common 
disease,  in  this  country  at  all  events,  and  it  is  perhaps  nowhere 
more  prevalent  than  in  the  neighbourhood  of  Edinburgh.  During 
the  past  ten  years  I  have  seen  in  hospital  and  consulting  practice 
thirty-three  cases  of  adult  myxcedema,  one  case  of  juvenile  myxoe- 
dema, and  six  cases  of  sporadic  cretinism — a  very  large  number 
for  any  individual  physician.  Before  the  thyroid  treatment  was 
introduced  I  used  frequently  to  see  well-marked  cases  of  myxce- 
dema in  the  streets.  At  that  time,  there  were  almost  always 
some  cases  of  the  disease  to  be  met  with  in  our  large  hospitals. 
The  thyroid  treatment  has  changed  all  this.  Well-marked  ex- 
amples of  the  disease  are  now  comparatively  rarely  met  with  in 
Edinburgh.  The  "  full-blown  cases,"  as  I  am  in  the  habit  of 
terming  them,  have  all  been  recognised  and  treated.  The  cases 
which  we  now  see  are,  with  rare  exceptions,  imperfectly  developed 
cases.  It  is  probable  that  in  the  future  the  fully  developed  cases 
will  seldom  be  met  with  except  in  remote  districts,  away  from  the 
centres  of  medical  education  and  thought. 

From  statements  made  to  me  by  several  medical  friends  in 
Dundee,  I  gather  that  the  disease  is  quite  as  prevalent  in  that  city 
as  in  Edinburgh.  The  disease  is  also  comparatively  common  in 
the  north  of  England — Dr  George  Murray  thinks  more  common  in 
this  than  in  other  parts  of  England.  The  Clinical  Society's  Report 
seemed  to  show  that  the  disease  was  very  rare  in  Ireland  ;  but  I 
feel  very  doubtful  as  to  this,  for  when  I  was  collecting  illustrations 
for  my  "  Atlas  of  Clinical  Medicine,"  I  found  that  there  were  three 
cases  in  the  town  of  Londonderry  alone. 

In  Germany,  America,  and  some  other  parts  of  the  world,  the 
disease  seems  to  be  much  less  common  than  it  is  here.  A  few 
years  ago,  Professor  Hoffmann  told  me  that  the  disease  was  rare  in 
Heidelberg.  Up  to  that  time  he  had  only  met  with  one  case  of  the 
disease.  At  the  same  time,  he  stated  that  within  the  past  few 
years  he  had  seen  eight  cases  of  acromegaly,  all,  with  one  or  two 
exceptions,  collected  from  a  radius  within  twenty  miles  round 
Heidelberg.  Now,  acromegaly  (which  seems  to  have  some  rela- 
tionship with  myxoedema),  although  probably  less  rare  than  is 
usually    supposed,    is    in    this    country    much    less    common    than 

T 


290  DISEASES   OF   THE   BLOOD   GLANDS. 

mvxcedema.*  In  some  parts  of  America  myxcedema  seems  to  be 
almost  unknown.  Dr  Mackenzie,  of  Cincinnati,  for  example,  tells 
me  that  he  has  never  seen  a  case  either  in  hospital  or  private  prac- 
tice, and  he  is  visiting  physician  to  a  hospital  which  contains  more 
than  four  hundred  beds. 

It  is  difficult  to  account  for  the  remarkable  prevalence  of  the 
disease  in  this  country,  unless  it  be  due  to  some  endemic,  telluric, 
or  climatic  condition.  Possibly  the  cold  and  damp  of  our  climate 
predisposes  to  the  production  of  the  disease.  And  in  confirma- 
tion of  this  it  may  be  stated  that  the  disease  seems  very  rare  in  hot 
and  tropical  climates.  I  have,  however,  met  with  one  case  of 
myxcedema  and  one  case  of  sporadic  cretinism  in  which  the 
disease  developed  in  India. 

Sex. — Myxcedema  is  at  least  six  times  as  frequent  (perhaps 
ten  times  as  frequent)  in  women  as  in  men.  Of  109  cases  tabu- 
lated in  the  Clinical  Society's  Report,  94  were  women  and  1 5  were 
men  ;  while  of  1 50  cases  tabulated  by  Drs  Henry  Hun  and  T. 
Mitchell  Prudden,  113  were  females  and  32  were  males,  the  sex  not 
being  stated  in  5.  Of  370  cases  analysed  by  Dr  George  Murray, 
322  were  women  and  48  were  men.  In  my  series  of  33  cases  of 
adult  myxcedema,  29  were  females  and  4  males ;  and  all  of  my  (7) 
cases  of  juvenile  myxcedema  and  sporadic  cretinism  were  females. 

In  its  preference  for  the  female  sex,  myxcedema  resembles  exoph- 
thalmic goitre.  Professor  Victor  Horsley  has  suggested  that  the 
greater  prevalence  of  myxcedema  and  exophthalmic  goitre  in  women 
is  due  to  the  fact  that  the  thyroid  gland  functionates  more  actively 
and  is  liable  to  more  sudden  variations  (ups  and  downs)  in  func- 
tional activity  in  the  female  than  in  the  male.  He  adds  : — "  It  is 
well  known  that  enlargement  of  the  thyroid  gland  is  not  uncommon 
in  women  during  menstruation  and  pregnancy  ;  and  it  may  be  laid 
down  as  a  pathological  law  that  the  greater  the  physiological  activity 
of  an  organ,  and  more  especially  the  greater  the  variability  of  that 
activity,  the  greater  the  liability  to  certain  diseased  processes." 

So  far  as  my  observation  enables  me  to  judge,  sporadic  cre- 
tinism is  also  much  more  common  in  girls  than  in  boys. 

Marriage  and   Child-bearing. — The  disease  seems  to    occur 

*  In  reference  to  this  point,  Dr  Sidney  Kuh  kindly  wrote  me  on  8th  March 
1893  as  follows  : — "  I  have  read  your  remarks  on  myxcedema  (Meeting  of  Edin- 
burgh Medico-Chirurgical  Society,  15th  February  1893),  in  which  you  refer  to  a 
statement  of  Professor  Hoffmann  that  myxcedema  is  very  rare  in  Heidelberg. 
Permit  me  to  state  that  I  have  seen  two  or  three  cases  of  the  disease  in  the 
Heidelberg  Insane  Asylum  (Clinic  of  Prof.  Kraepelin)  within  a  few  months,  in 
1892,  which,  I  think,  would  prove  that  your  conclusion  is  not  quite  correct." 


MYXCEDEMA.  29 1 

more  frequently  in  married  women  who  have  borne  families  than 
in  the  unmarried,  though  it  is  by  no  means  uncommon  in  single 
women.  Of  the  115  female  cases  analysed  by  Drs  Hun  and 
Prudden,  84  of  the  women  were  married  and  14  were  single  ;  while 
in  17  there  was  no  mention  made  of  this  point.  The  84  married 
women  had  had  more  than  300  children  and  29  miscarriages. 
In  my  29  cases  of  adult  myxcedema  in  females,  23  were  married 
and  6  were  single.  The  23  married  women  had  had  119  children, 
or  on  an  average  5.1  child  each.  Marriage,  therefore,  and  especially 
the  bearing  of  children,  seems  to  have  a  distinct  influence  in 
favouring  the  development  of  the  disease. 

Age. — Myxcedema  is  most  frequently  developed  during  the 
middle  periods  of  life — between  the  ages  of  35  and  45  ;  but  the 
symptoms  are  usually  so  insidious  in  their  mode  of  onset  that 
there  is  probably  a  tendency  to  over-estimate  the  age  at  which  the 
disease  actually  does  commence ;  in  other  words,  to  think  that 
it  begins  later  than  it  really  does.  According  to  Hun  and  Prud- 
den's  statistics,  the  average  age  at  which  the  disease  commenced 
in  seventy-six  women  was  38  and  in  twenty  men  42  years.  In  my 
own  33  cases,*  the  average  age  at  which  the  disease  commenced 
was  in  women  41  years  and  in  men  43  years.  But  the  disease  is 
by  no  means  confined  to  middle-aged  adults.  It  may  develop  at 
any  age,  and  it  is  comparatively  common  in  young  children,  for 
there  can  be  no  doubt  that  the  condition  which  is  termed  sporadic 
cretinism  is  merely  the  infantile  form  of  myxcedema.  In  stating 
that  sporadic  cretinism  is  the  infantile  form  of  myxcedema,  I  do 
not  mean  to  imply  that  the  pathological  process  (the  lesion  in  the 
thyroid  gland)  which  produces  myxcedema  and  sporadic  cretinism 
is  necessarily  one  and  the  same  in  all  cases.  Myxcedema  is  a 
clinical  condition  due  to  abolition  of  the  function  of  the  thyroid 
gland  ;  and  any  pathological  process  which  produces  arrest  of  the 
thyroid  secretion  will  produce  myxcedema.  In  some  cases  of 
infantile  myxcedema  (sporadic  cretinism),  the  condition  is  doubt- 
less due  to  congenital  absence  or  arrested  development  of  the 
thyroid  gland  during  intra-uterine  life  ;  in  others,  to  a  process  of 
cirrhotic  atrophy  similar  to  that  which  produces  myxcedema  in  the 
adult.  Myxcedema  very  rarely  indeed  develops  between  early 
childhood  and  the  age  of  20  ;  in  other  words,  the  "juvenile  "  form  of 
myxcedema,  as  I  term  it  (to  distinguish  the  condition  from  sporadic 


*  One  case  of  juvenile  myxcedema,  in  which  the  disease  seemed  to  com- 
mence at  the  age  of  10  years,  and  the  cases  of  infantile  myxcedema,  are  not 
included  in  this  calculation. 


292  DISEASES   OF   THE    BLOOD   GLANDS. 

cretinism  or  "  infantile  "  myxcedema),  is  very  rare.     One  case  only 
has  come  under  my  own  notice. 

The  disease  is  occasionally  met  with  in  old  people.  A  few 
years  ago  I  saw,  with  my  friend  Dr  Mackie  Whyte,  of  Dundee,  a 
woman,  aged  72,  who  was  suffering  from  the  disease.  In  her  case 
the  characteristic  symptoms  were  first  noticed  at  the  age  of  60. 
One  of  my  series  of  cases  treated  by  thyroid  extract  is  now  aged 
70,  and  another  at  the  time  of  her  death  was  aged  73. 

Hereditary  influence. — In  a  few  instances,  hereditary  predis- 
position can  be  directly  traced,  but  this  is  extremely  rare.  Amongst 
the  cases  analysed  by  the  committee  of  the  Clinical  Society  two 
were  sisters,  two  were  relatives,  and  in  one  the  father,  and  in 
another  the  mother,  probably  died  of  myxcedema.  Some  years  ago 
a  young  unmarried  lady,  aged  26,  was  sent  to  me  by  Dr  Halliday 
Croom,  suffering  from  all  the  characteristic  symptoms  of  the 
disease.  Some  ten  or  eleven  years  previously  I  had  seen,  with  Dr 
Croom,  the  paternal  uncle  of  this  patient  ;  his  case  was  quite 
typical  ;  he  died  from  the  disease,  and  I  examined  his  body  post- 
mortem. In  another  case,  seen  with  Dr  Aitchison  Robertson,  the 
mother  of  the  patient  had  died  some  years  previously  from 
myxcedema,  and  a  brother  had  a  swollen  heavy  face  suggestive  of 
myxcedema.  In  more  than  one  case  of  myxcedema  which  has 
come  under  my  notice,  a  sister  or  other  near  female  relative  of  the 
patient  had  suffered  from  exophthalmic  goitre.  In  rare  cases,  of 
which  Case  XVII.  is  an  example,  the  disease  follows  exophthalmic 
goitre. 

Other  predisposing  conditions. — With  regard  to  the  other 
conditions  which  predispose  to  the  production  of  the  disease,  little 
can  be  said.  In  a  considerable  proportion  of  the  cases,  the  sub- 
jects of  myxoedema  seem  to  inherit  a  tendency  to  nerve  disease. 
Tubercular  disease  also  seems  somewhat  more  common  in  the 
relatives  of  myxoedematous  patients  than  in  the  general  mass  of  the 
population.  Depressing  influences  of  all  kinds,  mental  strain, 
anxiety,  nerve  shock,  have  preceded  the  development  of  the  disease 
in  a  considerable  number  of  the  recorded  cases.  In  quite  a 
number  of  my  own  cases  (6  out  of  33)  the  patients  have  of  their  own 
accord  laid  great  stress  upon  this  point.  In  a  considerable  number 
of  cases  the  onset  of  the  disease  is  attended  with,  or  preceded  by, 
menorrhagia  ;  in  others,  by  an  excessive  loss  of  blood  after  de- 
livery. I  have  been  much  struck  with  the  frequent  history  of 
menorrhagia  in  my  own  cases — whether  that  was  a  cause  or  a  con- 
sequence of  the  disease  is,  however,  doubtful.  Some  authorities 
statu  that   a   tendency  to  haemorrhage    is    a    highly   characteristic 


MYXCEDEMA.  293 

feature  of  the  disease.  I  have  not  observed  this  in  any  one  of 
the  thirty-three  cases  which  have  come  under  my  notice,  though  in 
eight  there  was  menorrhagia  either  at  the  onset  or  during  the  course 
of  the  disease.  In  some  of  my  cases,  the  disease  developed  after 
influenza ;  in  one,  after  a  "  severe  illness,"  the  exact  nature  of 
which  I  could  not  ascertain ;  in  one  case,  after  confinement  without 
loss  of  blood  ;  in  another  case,  after  post-partum  haemorrhage  and 
mental  worry. 

Injuries,  and  especially  head  injuries,  have  in  some  instances 
been  blamed  as  a  cause  of  the  condition. 

It  can  hardly  be  questioned  that  in  the  human  subject  exposure 
to  cold  favours  the  development  of  the  disease  in  those  cases  in 
which  the  thyroid  gland  has  been  removed  by  operation,  just  as  it 
undoubtedly  does  in  the  lower  animals.  It  seems  certain,  too,  that 
exposure  to  cold  hastens  the  development  of  idiopathic  (primary) 
myxcedema,  and  aggravates  the  symptoms  once  the  disease  has 
become  established ;  but  whether  exposure  to  cold  favours  the 
degeneration  and  atrophy  of  the  thyroid  gland,  which  is  the  patho- 
logical substratum  of  the  disease,  is  another  matter.  It  is  not 
unlikely  that  this  is  so,  but  so  far  as  I  know  there  is  no  direct 
evidence  in  favour  of  such  a  proposition,  unless  the  great  prevalence 
of  the  disease  in  our  cold  and  inclement  climate  is  taken  as  a 
sufficient  proof. 

Morbid  Anatomy  and  Pathology. 

The  essential  pathological  lesion  in  myxcedema  is  degeneration 
and  atrophy  of  the  thyroid  gland.  That  the  disease  is  due  to 
diminution  or  abolition  of  the  function  of  the  thyroid  gland  is 
proved  by  the  following  facts  : — 

1.  In  the  bodies  of  patients  who  have  died  of  myxcedema,  the 
thyroid  gland  is  invariably  found  to  be  degenerated  and  usually 
atrophied  and  smaller  than  normal. 

In  some  cases,  though  degenerated  and  atrophied  as  regards  its 
secreting  structure,  the  thyroid  gland  is  enlarged.  This  was  the 
case  in  Dr  Mackie  Whyte's  patient  to  whom  I  have  previously 
referred.  The  same  condition  has  been  observed  in  some  other 
instances. 

2.  This  degeneration  and  atrophy  of  the  thyroid  gland  is  the 
only  constant  and  invariable  lesion  to  be  found  in  the  bodies  of 
patients  who  have  died  with  myxcedema  which  can  adequately 
account  for  the  symptoms  of  the  disease. 

3.  Total  extirpation  of  the  thyroid  gland  in  many  of  the  lower 
animals    is    followed    (provided    the   animal    survives   a   sufficient 


294  DISEASES   OF   THE   BLOOD   GLANDS. 

length  of  time)  by  symptoms  which  closely  resemble  and  appear  to 
be  identical  with  those  of  myxcedema  in  the  human  subject. 

4.  Total  extirpation  of  the  thyroid  gland  in  man  is  also  followed 
by  the  development  of  symptoms  identical  with  those  of  idiopathic 
(spontaneously  developed)  myxcedema. 

In  those  cases  in  which  the  symptoms  of  myxcedema  have  not 
been  developed  after  extirpation  of  the  thyroid  gland,  it  is  probable 
either  (a)  that  the  gland  was  not  entirely  removed,  or  (b)  that 
supernumerary  thyroid  glands  were  present,  and  that  they  were 
not  recognised  at  the  time  of  the  operation. 

5.  The  symptoms  of  myxcedema  rapidly  disappear,  and  the 
disease  can  be  completely  cured  and  kept  in  abeyance  by  the  intro- 
duction into  the  bodies  of  affected  persons,*  of  a  sufficient  quantity 
of  the  thyroid  secretion,  either  in  the  form  of  the  raw  gland,  in  the 
form  of  a  liquid,  or  of  a  solid  extract.  And,  what  is  still  more 
remarkable,  the  beneficial  effects  are  still  obtained  when  the  thyroid 
secretion  is  introduced  through  the  stomach,  either  in  the  form  of 
the  raw  or  partially  cooked  gland,  or  as  a  liquid  or  solid  extract. 

The  nature  of  the  lesion  of  the  thyroid  gland. — The  morbid 
change  in  the  thyroid  gland  which  produces  the  idiopathic  myxce- 
dema of  adults  seems  to  begin  as  a  small-celled  infiltration  of  the 
walls  of  the  vesicles,  which  is  accompanied  or  soon  followed  by 
epithelial  proliferation  in  the  vesicles  themselves.  In  a  more 
advanced  stage,  the  gland  becomes  converted  into  a  mass  of 
delicate  fibrous  tissue,  in  the  midst  of  which  clumps  of  small 
round  cells,  clearly  the  remains  of  the  vesicles,  are  scattered.^ 

Changes  in  other  organs  and  parts. — In  addition  to  these 
changes  in  the  thyroid  gland  itself,  pathological  alterations  are 
present  in  other  organs.  In  most  cases  in  which  the  condition  of  the 
pituitary  gland  has  been  noted,  the  gland  has  been  enlarged  ;  the 
thymus  gland  is  in  some  cases  also  enlarged  ;  well-marked  patho- 
logical changes  are  developed  in  the  skin  and  its  appendages  ; 
and  in  certain  cases  of  the  disease,  cirrhotic  changes  have  been 
found  in  the  kidney  and  blood  vessels  —  endarteritis  obliterans 
or  atheroma.  In  one  case  which  I  examined  some  years  ago, 
the  spinal  cord  was  markedly  shrunken  ;  and  it  is  probable  that 
more  detailed  and  accurate  investigation,  with  modern  methods  of 
staining  and  preparation,  will  show  definite  histological  changes 
in  the  nervous  tissues,  particularly  in  the  nerve  cells  ;  indeed,  it  is, 


*  Provided  that  the  patient  is  not  too  old,  that  the  heart  and  arteries  are 
sound,  and  that  there  are  no  associated  lesions  or  complications. 

+  Report  by  the  Committee  of  the  Clinical  Society  of  London,  p.  44. 


MYXCEDEMA.  295 

I  think,  highly  probable  that  minute  changes  are  present  in  all  of 
the  tissues  of  the  body. 

Most  of  the  pathological  changes  which  I  have  just  mentioned 
are  obviously  either  secondary  or  mere  associated  lesions  ;  they  are 
not  the  primary  and  essential  causes  of  the  disease. 

As  to  the  conditions  which  determine  the  atrophy  and  degenera- 
tion of  the  thyroid  gland,  which  is  the  primary  and  essential  lesion 
of  the  idiopathic  or  acquired  form  of  myxcedema  in  the  adult,  we 
are  at  present  ignorant.  As  I  have  already  stated,  exposure  to 
cold  seems  to  favour  the  production  of  the  disease  and  to  aggravate 
the  symptoms  when  the  disease  is  already  developed.  This  fact 
was  strikingly  demonstrated  by  two  experiments  made  by  Professor 
Horsley,  the  one  on  a  sheep,  the  other  on  a  donkey.  He  com- 
pletely removed  the  thyroid  gland  in  two  sheep.  The  result  in 
No.  1  was  survival,  without  the  production  of  symptoms  of 
myxcedema,  2\  years  after  the  removal  of  the  thyroid.  The  result 
in  No.  2  was  death  from  acute  myxcedema,  brought  on  by  accidental 
exposure  to  cold,  if  years  after  the  extirpation.  Professor  Horsley 
makes  the  following  statement  regarding  the  latter  case  : — 

"  The  fatal  case  in  the  second  sheep  is  one  of  much  interest,  since  it  entirely 
negatives  the  view  that  the  effects  of  total  extirpation  are  due  to  injury  of 
neighbouring  structures  in  the  course  of  the  operation,  and  proves  that  the 
myxedematous  state  is  produced  by  the  loss  of  the  thyroid.  It  is  worth  while, 
therefore,  to  mention  the  leading  features  in  this  instance.  The  thyroid  was 
removed  (3rd  October  1885)  with  the  usual  precautions,  and  primary  union  of 
the  wound  resulted.  The  sheep  emaciated,  and  was  weak  a  fortnight  later, 
but  its  temperature  was  normal  and  appetite  good.  No  marked  change  was 
observable  in  the  animal,  except  that  it  gradually  recovered  its  general  nutrition, 
and  apparently  became  more  stupid,  even  than  before  the  operation.  In  the 
meanwhile  the  wool  grew,  and  not  being  cut  covered  the  animal  very  thickly. 
In  view  of  the  approaching  summer  weather  it  was  shorn  in  the  first  week  of 
May  1887.  The  weather,  which  had  been  mild,  became  very  cold  ;  the  animal 
was  then  observed  to  become  ill,  it  lost  its  appetite,  then  exhibited  the  usual 
symptoms  of  the  acute  cachexia,  viz.,  spasms,  paralysis,  coma,  anaesthesia, 
tetanoid  contracture,  and  fall  of  temperature  to  250  C.  It  died  on  20th  May 
1887,  i.e.  569  days  after  the  operation.  The  post-mortem  examination  showed 
'  gelatinous  '  infiltration  of  all  the  subcutaneous  tissue,  which  under  the  micro- 
scope was  evidently  mucinous  degeneration  of  the  ground  substance,  and  by 
chemical  analysis  was  shown  to  be  actually  mucin.  The  thyroid  gland  had 
been  completely  removed.  In  this  instance  we  have  the  well-known  influence 
of  cold  evoking  the  phenomena  of  the  cachexia  in  its  most  acute  form.  It  is 
interesting  to  note  that  the  companion  animal,  sheep  No.  1,  which  was  similarly 
treated,  but  a  much  stronger  and  bigger  animal,  still  survives,  and  will  be  pre- 
served as  long  as  it  will  live.  Professor  Horsley  made  one  experiment  upon 
a  donkey,  which  supports  the  points  established  by  the  experiment  just  quoted 
of  sheep  No.  2.  'The  thyroid  was  removed  on  25th  August  1885.  After  the 
operation  the  animal  emaciated  in  spite  of  excessive  appetite,  became  weaker, 


296  DISEASES   OF   THE   BLOOD   GLANDS. 

lay  down,  and  the  temperature  was  low.  (Most  of  the  wound  healed  by  the 
first  intention,  the  remainder — about  one-sixth — by  suppuration  ;  cicatrisation 
was  complete  by  about  the  end  of  September  1885.)  After  the  general  appear- 
ance of  illness  had  lasted  two  months  the  nutrition  improved,  and  no  obvious 
change  was  noted  (the  psychical  analysis  being  difficult)  until  the  beginning  of 
March  1886,  when,  the  weather  becoming  suddenly  severely  cold,  the  animal 
fell  ill  ;  and  anorexia,  tremors,  fall  of  temperature,  &c,  occurring  in  the  order 
given,  death  with  all  the  characteristic  symptoms  occurred  within  a  week  of 
their  being  first  noted,  i.e.  205  days  after  operation.  Post-mortem. — The 
thyroid  gland  was  found  to  have  been  completely  removed.  All  tissues  and 
organs  appeared  normal.' " 

Pathological  Physiology. 

Two  theories  have  been  advanced  to  explain  the  exact  manner 
in  which  abolition  of  the  function  of  the  thyroid  gland  produces 
myxcedema. 

According  to  one,  the  thyroid  gland  secretes  and  pours  into 
the  blood  some  substance  or  substances  essential  for  the  healthy 
and  satisfactory  nutrition  of  the  tissues,  and  more  especially  of  the 
cerebral  and  nervous  tissues.  When  the  function  of  the  gland  is 
abolished  or  defective,  a  widespread  change  in  the  metabolism  of 
the  tissue,  more  particularly  in  the  skin  and  its  appendages  and  in 
the  nervous  tissues,  is  produced.  The  functional  alterations  which 
result  from  these  derangements  of  metabolism  and  from  the  minute 
structural  changes  which  are  produced  in  the  tissues  and  organs  of 
the  body  and  the  structural  and  functional  alterations  which  are  due 
to  the  pressure  of  the  myxcedematous  infiltration,  as  it  may  be 
termed,  on  the  tissue  elements  are  the  cause  of  the  symptoms  which 
characterise  the  disease. 

According  to  the  second  view,  the  function  of  the  thyroid  gland 
is  to  separate  from  the  blood  some  substance  or  substances  which, 
if  left  to  circulate  in  the  blood,  exert  a  poisonous  influence  upon 
the  tissues,  more  especially  upon  the  cerebral  and  nervous  tissues. 
Atrophy  and  abolition  of  the  function  of  the  gland  lead,  according 
to  this  view,  to  a  kind  of  intoxication  which  in  some  respects  may 
be  compared  to  chronic  uraemia.  As  a  result  of  this  intoxication, 
the  nervous  and  other  tissues  degenerate  and  the  symptoms  of  the 
disease  are  produced. 

There  can,  I  think,  be  little  doubt  that  the  former  view  is  the 
correct  one  ;  this  is  shown,  I  think,  by  the  beneficial  effects  which 
result  in  cases  of  myxcedema  and  sporadic  cretinism  from  thyroid 
feeding — even  from  the  introduction  into  the  stomach  of  a  few 
grains  of  the  dried  extract. 

That  the  thyroid  gland  is  in  some  manner  or  another  (either 


MYXCEDEMA.  297 

directly  or  indirectly)  concerned  in  the  regulation  of  the  metabolism 
of  mucin  or  of  substances  which  form  mucin,  or  that  it  is  concerned 
in  separating  from  the  blood  some  substance  or  substances  which 
either  directly  or  indirectly  (possibly  through  the  nervous  system) 
favour  the  production  of  mucin  in  the  tissues,  seems  proved  by  the 
following  facts  : — 

In  Dr  Ord's  original  case,  an  excessive  quantity  of  mucin  was 
found  in  the  subcutaneous  and  other  tissues  ;  and  although  most  of 
the  analyses  which  have  been  subsequently  made  have  failed  to 
confirm  this,  at  all  events  in  the  same  degree,  it  seems  probable 
that  during  the  "swollen  stage"  of  the  disease  such  excess  is 
present.  And  here  it  may  be  noted  that  in  some  cases  of  myxoedema 
during  active  thyroid  treatment,  large  quantities  of  mucus  are 
excreted  by  the  kidneys.  In  one  of  my  cases,  for  example,  I  state 
in  the  clinical  report : — "  The  amount  of  mucus  was  quite  extra- 
ordinary ;  it  reached,  in  the  form  of  a  gelatinous-looking  mass,  like 
a  coagulum,  almost  to  the  top  of  the  tall  urine  glass  in  which  the 
urine  was  placed."  I  have  observed  the  same  result,  though  in  less 
degree,  in  more  than  one  other  case. 

After  extirpation  of  the  thyroid  gland  in  the  lower  animals  the 
amount  of  mucin  in  the  tissues  is  in  some  instances  enormously 
increased. 

Professor  Victor  Horsley  found  that  after  total  extirpation  of 
the  thyroid  gland  the  secretion  from  the  parotid  gland,  which  under 
normal  circumstances  contains  no  mucin,  may  contain  large  quanti- 
ties of  mucin. 

It  is  important  to  note  that,  while  in  acute  experimental 
myxoedema  the  tissues  contain  a  large  excess  of  mucin,  in  chronic 
experimental  myxoedema  no  such  excess  is  found.  In  chronic 
experimental  myxoedema,  fibroid  or  cirrhotic  changes  in  the  tissues 
seem  to  take  the  place  of  the  mucinous  degeneration  which  occurs 
in  the  acute  form  of  the  disease.  These  facts  perhaps  explain  the 
result  of  different  analyses  in  the  primary  and  idiopathic  myxoedema 
of  man  ;  for  while  in  Dr  Ord's  case  (which  died,  be  it  observed, 
during  the  swollen  stage  of  the  disease)  a  large  excess  of  mucin  was 
found  in  the  skin  and  subcutaneous  tissues,  in  other  cases  which 
have  since  been  analysed  no  such  excess  was  found.  But  in  these 
chronic  cases,  fibroid  and  cirrhotic  changes  in  the  skin  and  viscera 
have  been  invariably  observed. 

From  these  statements  it  will  be  gathered  that  recent  observa- 
tions have  confirmed  the  view,  which  physiologists  have  long  held, 
that  the  thyroid  gland  is  a  blood  gland,  and  that  the  thyroid 
secretion  is  essential  for  the  proper  nutrition  of  the  body.      I  would 


298  DISEASES   OF   THE   BLOOD   GLANDS. 

particularly  emphasise  the  fact  that  this  great  advance  in  our 
physiological  and  pathological  knowledge,  which  has  thrown  a 
flood  of  light  upon  the  function  of  the  so-called  blood  glands  and 
ductless  glands,  and  has  opened  up  such  a  wide  field  for  scientific 
research  and  therapeutic  investigation,  is  very  largely  the  result  of 
clinical  observation. 


Clinical  History. 

Onset  and  Mode  of  Development. — The  onset  of  myxcedema 
is  usually  very  slow  and  insidious,  though  in  exceptional  cases  the 
symptoms  appear  to  develop  rapidly.  In  a  case  recorded  by 
Charcot,  for  example,  the  disease  was  ushered  in  by  attacks  of 
shivering,  and  in  the  first  case  reported  by  Ord,  the  onset  of  the 
disease  was  attended  with  shivering,  and,  according  to  the  patient, 
with  the  passage  of  bloody  urine.  In  one  of  my  cases  (Case  IV.), 
the  patient,  an  intelligent  young  lady,  26  years  of  age,  stated  that 
the  swelling  of  the  face,  and  the  other  symptoms  of  the  disease 
developed  in  the  course  of  a  few  days  after  an  attack  of  influenza. 
In  another  case  (Case  XXVIII.),  all  the  characteristic  symptoms 
were  developed  in  the  course  of  four  months. 

But  in  most  cases  such  as  these,  in  which  the  myxedematous 
symptoms  appear  to  develop  rapidly,  it  is  highly  probable  that  the 
disease  has  been  in  existence  in  an  unrecognised  form  for  some 
time  previously.  In  my  own  case,  for  example,  I  found,  on  careful 
cross-examination  of  the  patient,  that  for  two  or  three  years  before 
the  attack  of  influenza  to  which  she  attributed  the  onset  of  the 
disease,  she  had  been  unduly  susceptible  to  cold.  In  this,  as 
in  many  other  cases,  the  date  at  which  the  symptoms  are  first 
perceived  by  the  patient  is  often  a  very  fallacious  guide  to  the 
actual  date  of  onset  of  the  disease.  The  patient  naturally  dates 
the  onset  of  the  disease  from  the  time  at  which  he  becomes 
conscious  of  the  symptoms,  or  at  which  the  results  of  the  disease 
first  become  distinctly  noticeable  to  others  ;  but  the  disease  may 
have  been  slowly  and  gradually  developing  for  years  before  the 
symptoms  are  sufficiently  marked  to  attract  attention. 

Initial  Symptoms. — A  feeling  of  intense  lassitude  and  debility, 
a  repugnance  to  exertion  both  of  body  and  mind,  increased  bulk  of 
the  body,  an  increased  susceptibility  to  cold,  and  dryness  of  the 
skin,  are,  so  far  as  my  observation  enables  me  to  judge,  usually  the 
first  symptoms.  In  some  cases,  headache,  usually  frontal,  is  an 
early  symptom.  In  consequence  of  the  debility  and  disinclina- 
tion for   exertion,  most  myxedematous  patients  feel  unable,  even 


MYXCEDEMA.  299 

in  the  earlier  stages  of  the  disease,  to  attend  to  their  household 
duties.  ( 

Debility  and  lassitude  were  prominent  symptoms  in  every  one 
of  my  33  cases  of  adult  myxoedema. 

As  the  disease  advances,  a  striking  change  takes  place  in  the 
appearance  of  the  patient,  and  when  the  myxcedematous  condition 
is  fully  developed  the  physiognomy  is  highly  characteristic. 

The  body  as  a  whole  is  increased  in  bulk,  the  face,  trunk,  and 
limbs  all  being  involved.  The  increase  is  due  to  a  solid  oedema. 
The  parts  affected  by  this  oedema  do  not  pit  on  pressure,  and,  it  is 
said,  do  not  exude  a  watery  fluid  on  puncture  ;  though,  as  has  been 
previously  stated,  ordinary  dropsical  swelling  (watery  oedema)  of 
the  feet  and  ankles  is  sometimes  also  present.  Ordinary  dropsy 
(oedema  of  the  feet  and  ankles)  was  present  in  8  of  my  33  cases  of 
adult  myxoedema. 

Facial  Appearance. — On  looking  at  the  face,  one  is  at  once 
struck  with  the  heavy  stolid  expression  of  countenance.  The  face 
is  full,  coarse,  broad-looking,  and  round;  it  has  been  termed  "moon- 
shaped."  As  a  whole  it  looks  puffy  and  swollen.  In  many  cases? 
the  wrinkles  are  flattened  out,  but  this  is  by  no  means  always  the 
case.  The  skin  of  the  eyelids  in  particular  has  a  translucent  and 
wax-like  appearance.  Baggy  swellings,  highly  suggestive  of  a 
dropsical  oedema,  are  often  present  beneath  the  lower  eyelids. 
These  swellings  are  at  first  sight  highly  suggestive  of  Bright's 
disease.  The  upper  lids  in  many  cases  droop  over  the  eyeballs ; 
and,  in  order  to  prevent  the  loss  of  sight  which  is  occasioned  by  the 
falling  of  the  upper  lids  over  the  pupils,  there  is  often  a  compensa- 
tory elevation  of  the  eyebrows  and  transverse  wrinkling  of  the 
forehead.  The  same  compensatory  elevation  of  the  eyebrows  is 
seen  in  cases  of  paralytic  ptosis.  In  one  of  my  cases,  the  upper 
lids  were  so  much  swollen  that  they  completely  covered  the  eye- 
balls ;  the  patient,  in  order  to  see,  had  to  raise  the  swollen  lid  with 
the  finger  so  as  to  expose  the  pupil.  The  upper  eyelids  are  either 
swollen  or  wrinkled -looking.  The  cheeks  are  in  some  cases 
pendulous  ;  in  describing  his  condition  before  treatment,  one  of  my 
patients  wrote  me,  "  I  had  great  bags  under  my  eyes  and  my  cheeks 
were  puffy  and  hanging,  bobbing  up  and  down  as  I  walked  along." 
The  lips  are,  in  the  great  majority  of  cases,  swollen  and  usually  of 
a  bluish  or  purple  colour  ;  the  lower  lip  in  particular  is  unusually 
full ;  it  usually  feels  firm,  tense,  and  elastic  ;  to  the  touch  it  re- 
sembles more  or  less  closely  a  piece  of  indiarubber.  The  nose  is 
broad  and  coarse-looking.  The  ears  are  in  some  cases  large  and 
swollen. 


300  DISEASES   OF   THE   BLOOD   GLANDS. 

Dr  Ord  states  that  "  the  total  effect  (of  these  changes  in  the 
face)  is  that  of  a  mask  of  sorrowful  immobility."  * 

As  I  have  just  remarked,  the  appearance  of  the  eyelids  and  the 
swollen  condition  of  the  face  are  highly  suggestive  of  Bright's 
disease ;  and  there  is  no  doubt  that  before  the  clinical  features  of 
the  disease  were  clearly  differentiated,  cases  of  myxcedema  were 
often  diagnosed  as  cases  of  kidney  disease.  But  on  close  scrutiny, 
the  facial  appearance  is  very  different  from  that  of  kidney  disease. 
In  typical  cases  of  myxcedema,  a  pink  blush  is  present  on  each 
cheek  ;  in  exceptional  cases,  the  blush  is  not  confined  to  the  cheeks ; 
in  one  of  my  cases  it  involved  the  nose ;  in  two  other  cases  a  bright 
pink  blush  was  diffused  over  the  whole  of  the  cheeks  and  nose. 
The  colour  of  the  face,  too,  is  usually  different  from  that  of  Bright's 
disease.  The  skin  has  in  many  cases  a  dingy  yellow  tinge  (except 
about  the  eyelids,  where  it  is  usually  translucent  and  wax-like), 
quite  different  from  the  white  pallor  which  is  such  a  striking  feature 
in  those  cases  of  Bright's  disease  in  which  the  face  is  much  swollen ; 
while  the  baldness  of  the  scalp  or  the  thin,  dry,  harsh  condition  of  the 
hair,  the  dirty  brown  encrustation  of  the  scalp,  and  the  thinness  or 
absence  of  the  eyebrows,  which  are  such  important  characteristics 
of  the  disease  in  its  advanced  stages,  are  absent  in  Bright's  disease. 

The  tawny  yellow  discoloration  of  the  skin  is  chiefly  seen  on 
the  face,  neck,  and  other  parts  of  the  body  which  are  exposed  to 
the  atmosphere.  This  discoloration  may  persist  after  the  cedema- 
tous  condition  has  completely  disappeared  under  treatment.  Yellow 
discoloration  of  the  skin  of  the  face  was  present  in  32  of  my  33 
cases  of  adult  myxcedema. 

In  my  33  cases  of  adult  myxcedema,  a  pink  blush  was  present 
on  the  cheeks  in  26  cases  ;  in  the  4  male  cases  included  in  the 
series,  a  pink  blush  was  present  in  only  one  case. 

I  have  now  referred  to  the  more  important  changes  which 
myxcedema  produces  in  the  face.  The  alterations  which  occur  in 
other  parts  of  the  body  are  no  less  striking  and  characteristic. 

The  body  as  a  whole,  is  increased  in  bulk,  and  has  a  clumsy, 
heavy  appearance.  In  many  cases,  the  tongue  is  large  and  swollen, 
some  patients  say  that  it  feels  too  large  for  the  mouth.  The 
gums,  buccal  mucous  membrane,  the  fauces,  uvula,  pharynx,  and 
larynx  are  in  many  cases  also  cedematous.  The  swelling  of  the 
soft  parts  at  the  back  of  the  mouth  may  be  so  considerable  that 
the  patient  may  experience  considerable  difficulty  in  swallowing  ; 
some  patients  complain  of  a  choking  feeling  when  they  swallow. 

"  Lancet,"  12th  Nov.  1898,  p.  1243. 


MYXCEDEMA.  301 

The  neck  is  usually  broad  and  thick.  Puffy  elastic  swellings, 
which  are  usually  thought  to  be  due  to  localised  collections  of  fat, 
are  in  many  cases  present  at  the  root  of  the  neck  above  the 
clavicles.  These  elastic  supra-clavicular  swellings  are  usually  more 
marked  in  children  (cases  of  sporadic  cretinism)  than  in  adults. 
They  were  present  in  22  of  my  33  cases  of  adult  myxcedema. 

Although  the  neck  is  usually  short,  thick,  and  swollen,  the  rings 
of  the  trachea  can  generally  be  very  distinctly  felt ;  in  the  great 
majority  of  cases  of  the  disease  no  evidence  of  the  thyroid  can  be 
detected  during  life.  This  is  just  what  we  would  expect,  for  in  the 
great  majority  of  cases  of  myxcedema  the  thyroid  gland  is  markedly 
atrophied  ;  while  in  the  juvenile  form  of  the  disease  it  may  be 
altogether  absent.  In  those  exceptional  cases  in  which  the  thyroid 
is  present  or  enlarged,  its  structure  is  altered  and  destroyed — in 
other  words,  the  gland  is  functionally  inert. 

In  none  of  my  cases  of  myxcedema  or  sporadic  cretinism  could 
the  thyroid  gland  be  felt. 

I  may  say  in  passing  that  it  is  very  difficult  to  determine  by 
palpation  during  life  whether  the  thyroid  is  actually  present  or 
not.  This  difficulty  was  very  clearly  realised  at  a  post-mortem 
examination  on  a  case  of  myxcedema  which  I  made  in  conjunc- 
tion with  Dr  Thomson  a  few  years  ago.  In  that  case,  even  after 
deflecting  the  skin  of  the  neck,  we  were  unable  to  feel  the  thyroid 
body ;  but  on  further  dissection,  we  found  that  the  gland  was 
present.  At  first  sight,  it  looked  of  normal  size  ;  its  superficial 
extent  was  quite  equal  to  that  of  a  normal  thyroid  ;  but  it  was  so 
thin,  soft,  and  flabby,  and  so  closely  applied  to  the  trachea,  that, 
even  after  the  skin  had  been  deflected,  it  could  not  be  differentiated 
by  palpation  from  the  rings  of  the  trachea  with  which  it  lay  in  close 
contact. 

The  hands  are  enlarged  and  broad — "  spade-like  "  as  it  has 
been  termed.  The  fingers  are  broad,  fiat,  and  thick  ;  many  patients 
complain  of  their  inability  to  perform  fine  movements  (button  their 
clothes,  sew,  etc.)  ;  some  patients  say  that  they  cannot  close  the 
hand  in  consequence  of  the  swelling.  The  feet  present  similar 
changes  ;  they  are  broad  and  thick.  The  abdomen  is  usually  full 
and  large,  and  the  trunk  as  a  whole  looks  markedly  increased  in 
size.     The  vulva  and  external  genitals  are  in  some  cases  swollen. 

In  my  33  cases  of  adult  myxcedema,  increased  bulkiness  of  the 
body  as  a  whole  was  present  in  30  cases  ;  swelling  of  the  face  was 
present  in  32  cases  ;  of  the  hands  in  27  cases  ;  of  the  feet  in  26 
cases  ;  of  the  abdomen  in  29  cases  ;  of  the  tongue  in  27  cases ;  and 
of  the  throat  in  19  cases. 


302  DISEASES   OF   THE   BLOOD   GLANDS. 

The  increased  bulk  of  the  body  and  the  swollen  condition  of 
the  tissues,  which  are  such  striking  features  of  the  disease,  are  not 
the  result  of  an  ordinary  oedema,  such  as  the  oedema  of  cardiac  or 
renal  dropsy,  which  pits  on  pressure  and  exudes  fluid  on  puncture, 
but  of  a  solid  oedema,  which  in  the  early  stages  of  some  cases  at 
least,  is  associated  with  a  notable  increase  of  mucin  in  the  tissues. 
But  as  Drs  Hun  and  Prudden  have  pointed  out,  the  peculiar  nature 
of  the  oedema  does  not  always  depend  upon  an  infiltration  of  the 
skin  with  mucin.  They  explain  the  solid  character  of  the  oedema 
and  the  absence  of  pitting  on  pressure  in  the  following  manner  : — 

"A  possible  explanation  of  the  fact  that  in  myxoedema  the  skin,  although 
oedematous,  does  not  pit  on  pressure  is  contained  in  Dr  Prudden's  observations, 
that  the  separation  of  the  fibres,  and  the  dilatation  of  the  lymph  spaces  in  the 
skin  of  the  two  myxedematous  cases  which  he  examined,  were  in  those  super- 
ficial layers  of  the  corium  in  which  inter-fibrillary  spaces  are  much  smaller,  and 
the  interlacement  of  the  fibres  much  finer,  than  in  the  deeper  layers,  which  seem 
more  frequently  to  be  the  seat  of  ordinary  cedema.  From  these  smaller  spaces, 
surrounded  by  a  finer  network  of  interlacing  fibres,  fluid  is  neither  so  easily 
driven  by  pressure,  nor  so  easily  affected  by  gravity,  as  it  is  from  larger  spaces 
surrounded  by  a  coarse  network  of  fibres.  Probably  in  this  difference  in  the 
situation  of  the  fluid  lies  the  difference  between  the  swelling  of  the  skin  in 
myxcedema  and  in  ordinary  cedema."  * 

I  have  already  stated  that  in  some  cases  of  the  disease,  and 
chiefly  in  the  later  stages,  a  true  watery  cedema  is  present,  especially 
about  the  ankles. 

Such  are  the  gross  alterations  and  the  more  striking  changes  in 
the  physiognomy  which  myxcedema  produces  in  its  advanced  and 
fully  developed  stages.  When  we  come  to  study  the  condition 
more  minutely,  we  find  that  the  nutrition  of  the  skin  and  its 
appendages  is  profoundly  modified,  and  the  functional  activity  of 
the  nervous  apparatus  markedly  impaired. 

The  Condition  of  the  Skin  and  its  Appendages.— The  skin 
is  coarse,  harsh,  dry,  rough,  and  scaly  looking.  It  may  be  split  up 
by  superficial  wrinkles  and  cracks  into  lozenge-shaped  areas  not 
unlike  those  which  are  seen  in  some  cases  of  ichthyosis.  In  one  of 
my  cases  I  have  noted  that  when  the  finger  was  passed  over  the 
skin  of  the  forearm  it  felt  like  a  piece  of  sandpaper,  and  in  another 
as  rough  as  a  file.  The  skin  of  the  heels  in  some  cases  becomes 
greatly  thickened  ;  one  of  my  patients  stated  that  he  "  used  to  pare 
it  with  a  big  iron  file."  In  one  case  there  was  distinct  ichthyosis  of 
the  heels.  In  several  cases  eczematous  eruptions,  both  dry  and 
moist,  have  been  present. 

*  "  International  Medical  Journal,"  August  1SS8,  p.  152. 


MYXCEDEMA.  303 

In  all  of  my  33  cases  of  adult  myxcedema,  the  skin  was  harsh 
and  dry  ;  and  in  32  of  the  33  cases  there  was  absence  of  sweating. 

The  electrical  resistance  of  the  skin  is,  as  one  might  expect,  very 
greatly  increased  ;  and  this,  be  it  observed,  is  the  very  reverse  of 
the  condition  which  obtains  in  exophthalmic  goitre. 

In  well-marked  cases  of  myxcedema  the  secretion  of  sweat  is 
very  much  diminished  or  altogether  in  abeyance.  The  absence  of 
sweating  is  a  very  characteristic  feature  of  the  disease,  though  in 
some  cases  the  palms  may  occasionally  feel  moist.  The  sebaceous 
secretion  is  also  in  many  cases  said  to  be  arrested  or  very  much 
diminished.  Flat  moles  and  warts  are  sometimes  developed  on  the 
face,  neck,  etc.  In  some  cases,  stalked  moles  are  also  present.  In 
one  of  my  cases,  a  projecting  swelling  of  some  size,  like  a 
stalked  wart,  projected  from  the  gum  ;  and  in  another  case,  a  flat 
button-like  wart  was  present  on  the  dorsum  of  the  tongue  close  to 
the  tip. 

The  hair  becomes  thin,  dry,  brittle,  and  harsh  ;  in  many  cases, 
the  eyebrows  are  entirely  wanting ;  in  the  advanced  stages  of  the 
disease,  the  scalp  may  be  almost  entirely  bald,  and,  whether  this  is 
so  or  not,  it  is  usually  covered  with  dirty  brown  crusts.  This 
encrustation  of  the  scalp  is  of  considerable  diagnostic  importance. 
On  one  occasion  I  recognised  the  presence  of  myxcedema  in  the 
person  of  a  gentleman  who  was  sitting  immediately  in  front  of  me 
in  church,  by  the  coarseness  of  the  skin  of  the  back  of  his  neck,  the 
dry,  scanty,  ragged  character  of  the  hair  on  the  back  of  his  head, 
and  the  dirty-looking  brown  patches  which  were  present  on  his 
scalp.  The  correctness  of  my  opinion  was  amply  confirmed  when 
I  obtained  a  full  view  of  his  face,  for  it  was  in  every  way  typical 
and  characteristic  of  the  disease.  It  is  often  possible  to  recognise 
myxcedema  merely  by  looking  at  the  back  of  the  neck  and  scalp. 
The  thin,  ragged,  dry  condition  of  the  hair,  the  shrivelled,  yellow, 
wrinkled  appearance  of  the  skin  at  the  back  of  the  neck,  and  the 
dirty  brown  crusts  or  scales  on  the  scalp  have  in  more  than  one 
case,  in  addition  to  that  which  has  been  mentioned  above,  enabled 
me  to  recognise  the  disease  before  I  had  the  opportunity  of  looking 
at  the  patient's  face. 

In  some  cases,  the  colour  of  the  hair  changes  as  the  disease 
advances  ;  in  one  of  my  cases  the  hair,  which  in  health  was  brown, 
became  black ;  the  change  was  so  marked  that  the  patient's  brother 
thought  she  was  dyeing  it.  In  this  case,  the  hair  soon  began  to 
regain  its  natural  brown  colour  under  thyroid  treatment.  In 
another  case,  the  hair,  which  was  nut-brown  before  the  disease 
commenced,  became  so  black  after  a  course  of  thyroid  treatment 


304  DISEASES   OF   THE   BLOOD   GLANDS. 

that  the  patient's  sister  said  to  her  children,  "Why  is  your  mother 
dyeing  her  hair?"  In  several  other  cases,  the  luxuriant  crop  of 
hair  which  developed  after  the  myxcedematous  symptoms  had  been 
removed  by  the  administration  of  thyroid  extract  was  dark  and 
black  ;  in  one  case  in  which  this  took  place  the  patient  was  an  old 
woman  66  years  of  age. 

In  my  33  cases  of  adult  myxcedema,  loss  of  hair  was  present  in 
31,  and  encrustation  of  the  scalp  in  19  cases. 

In  some  cases,  the  nails  become  dry  and  lustreless,  brittle, 
ragged  or  cracked  ;  the  teeth  are  apt  to  become  carious  and  loose  ; 
in  some  cases  they  drop  out. 

The  altered  nutrition  of  the  skin  and  its  appendages  is  asso- 
ciated with,and  doubtless  depends  upon, definite  histological  changes, 
which  are  by  the  Committee  of  the  Clinical  Society  described  as 
follows  : — 

"  Very  marked  changes  are  seen  in  the  majority  of  cases  and  the  changes 
were  very  similar,  whatever  the  region  of  the  body  examined.  In  the  coiled 
tubes  of  the  sweat  glands,  the  epithelium  becomes  swollen,  then  nuclear  prolifera- 
tion takes  place,  and  the  lumen  of  the  tubes  becomes  obliterated.  In  the  later 
stages,  a  nucleated  fibrous  growth  is  seen  in  the  tissue  outside  the  tubes.  The 
change  in  the  sebaceous  glands  resembles  very  closely  that  in  the  sudoriparous 
glands,  and  is  probably  identical  with  it.  The  sebaceous  glands  are  represented 
by  irregular  masses  of  nuclei,  and  sometimes  there  are  cellular  accumulations  in 
the  tissues  outside  them.  These  cellular  accumulations  in  some  cases  seem  to 
undergo  partial  or  complete  absorption.  Around  the  hair-follicles  a  nuclear 
growth  is  apt  to  develop,  and  external  to  this  growth  an  abundant  nucleated 
fibrous  tissue  is  sometimes  seen.1'* 

In  some  cases,  there  is  an  increased  flow  of  saliva  from  the 
mouth,  especially  at  night;  whether  this  is  due  to  an  actual  increase 
of  the  amount  of  saliva  secreted  or  merely  to  the  fact  that  the  saliva 
which  is  secreted  flows  out  of  the  mouth  instead  of  being  swallowed 
is,  however,  doubtful.  In  other  cases,  the  nose  or  eyes  "run  "  with- 
out any  apparent  cause.  One  of  my  patients  stated,  "  My  eyes 
were  constantly  weeping  and  my  nose  running." 

This  (?)  increase  of  the  salivary  secretion  and  of  the  discharge 
from  the  nose  and  eyes  is  in  remarkable  contrast  with  the  dimin- 
ished or  abolished  secretion  of  sweat. 

In  my  33  cases  of  adult  myxcedema,  running  at  the  eyes  and 
nose  was  noted  in  3  cases,  and  increased  salivary  secretion  in  4 
cases. 

The  condition  of  the  motor  nerve  apparatus. — The  stolid, 
heavy-looking,  and  puffy  appearance  which  the  face  presents  reflects 

*  "  Medico-Chirurgical  Transactions,"  Vol.  lxi.,  p.  60. 


MYXCEDEMA.  305 

the  condition  of  the  sensorium.  One  of  the  most  striking  features  of 
the  disease  in  its  fully  developed  stages  is  the  slowness  with  which 
all  the  cerebral  processes,  especially  speech  and  muscular  move- 
ments, are  carried  out. 

The  gait  is  heavy  and  clumsy  ;  I  am  in  the  habit  of  terming  it 
"  hippopotamus-like."  The  muscular  power  is  markedly  impaired. 
Some  patients  experience  from  time  to  time  a  sudden  giving  way 
in  the  legs.  In  consequence  of  the  feebleness  of  the  muscles  of 
the  neck,  and  perhaps  also  of  the  sleepy  apathetic  condition,  the 
head  may  fall  down  on  to  the  sternum.  Dr  Ord  seems  to  lay 
considerable  stress  on  this  symptom.  I  noted  its  presence  in  2  only 
of  my  33  cases. 

In  most  cases,  the  patients  have  difficulty  in  performing  fine 
movements  with  the  fingers  ;  this  may  no  doubt  be  due  to  several 
different  causes  (i.e.,  swelling  of  the  fingers,  defective  sensibility,  want 
of  cerebral  concentration  and  attention,  deficient  muscular  power, 
inco-ordination),  or  a  combination  of  some  of  these  conditions. 

The  articulation  is  slow  and  measured  ;  the  tone  of  voice  is 
monotonous,  thick,  "  leathery,"  as  it  has  been  termed,  harsher  and 
hoarser  than  it  is  in  health;  the  patient  often  speaks  as  if  she  had 
something  in  the  mouth.  Patients  who  have  been  in  the  habit  of 
singing  find  that  with  the  development  of  the  disease  they  lose 
their  voice. 

Characteristic  thickness  of  speech  was  present  in  31  of  my  33 
cases  of  adult  myxcedema. 

These  alterations  in  movement,  and  in  speech,  seem  to  depend 
partly  upon  the  increased  bulk  of  the  body  and  limbs,  and  on  the 
swelling  of  the  lips,  tongue,  palate,  and  larynx,  and  partly  upon  the 
slowness  with  which  the  motor  nerve  apparatus  functionates.  The 
swelling  of  the  tongue  and  fauces  also,  in  part  at  least,  accounts 
for  the  difficulty  in  swallowing  which  is  complained  of  by  some 
patients. 

The  condition  of  the  cerebral  and  mental  functions. — All  the 
-cerebral  actions  of  myxcedematous  patients  appear  to  be  carried 
out  in  an  unusually  slow  and  deliberate  manner.  After  being 
asked  a  question,  they  often  take  an  extraordinarily  long  time  to 
answer  it;  the  ''reaction  time"  is  no  doubt  greatly  prolonged. 
The  acuteness  of  all  the  higher  cerebral  activities  is  blunted.  In 
most  of  the  cases  which  have  come  under  my  own  notice,  the 
memory  and  mental  activity  were  more  or  less  impaired.  The 
patients  often  complain  that  it  is  an  effort  to  think.  My  artist,  Mr 
Williamson,  who  has  painted  several  cases  for  me,  volunteered  the 
statement  that  myxcedematous  patients  are  remarkably  good  sitters ; 

u 


306  diseases  of  the  blood  glands. 

they  will  remain  for  a  long  time,  sometimes  for  hours  together,  in 
the  same  position  without  uttering  a  word  and  without  exhibiting 
any  change  of  expression.  In  consequence  of  the  mental  and  bodily 
inertia,  the  subjects  of  myxcedema  are  apt  to  keep  to  themselves 
and  to  shun  society.  This  is  perhaps,  as  Murray  has  suggested,  one 
reason  why  they  are  apt  to  become  morose,  depressed  and  melan- 
cholic. 

In  31  of  my  33  cases  of  adult  myxcedema,  the  memory  was 
more  or  less  impaired. 

This  slowness  of  thought  and  action  is  also  very  striking  in 
many  cases  of  sporadic  cretinism.  Children  affected  with  sporadic 
cretinism  often  sit  for  hours  perfectly  quiet,  apparently  taking  no 
notice  of,  or  interest  in,  their  surroundings,  and  yet  quite  happy, 
comfortable,  and  contented,  so  long  as  they  are  sitting  in  the  sun 
or  before  a  hot  fire. 

It  should  further  be  noted  that  in  many  cases  of  myxcedema 
there  is  an  excessive  tendency  to  sleep.  In  one  of  my  cases, 
the  patient,  a  medical  man,  stated  that  he  was  always  dreadfully 
sleepy,  that  he  could  hardly  keep  his  eyes  open  when  going  his 
rounds,  and  whenever  he  got  into  his  gig  he  used  to  drop  off  to 
sleep. 

In  my  33  cases  of  adult  myxcedema  the  patients  slept  well  in 
23  and  badly  in  6  cases  ;  in  the  remaining  4  cases  the  condition  of 
sleep  is  not  mentioned.  In  2  cases,  sleep  was  disturbed  by  very 
unpleasant  dreams. 

The  placidity  and  stolidity  of  myxcedematous  patients  con- 
trasts very  remarkably  with  the  perpetual  unrest  and  hyperex- 
citability  of  patients  affected  with  exophthalmic  goitre.  After  I 
have  described  exophthalmic  goitre,  I  will  point  out  the  difference 
between  the  two  diseases  in  more  detail.  But  I  may  here  say 
that  nervousness,  tremor,  and  unrest  are  striking  features  of  ex- 
ophthalmic goitre  ;  whereas,  stolidity  and  placidity  are  character- 
istic features  of  myxcedema.  It  should,  however,  be  stated  that  in 
some  cases  the  patients  state  that  they  are  more  easily  agitated 
and  "  put  about "  than  formerly. 

In  some  cases  of  myxcedema  more  profound  mental  alterations 
(delusions,  hallucinations,  insanity,  which  may  take  the  form  of 
acute  or  chronic  mania,  though  more  frequently  of  melancholia 
or  dementia)  are  developed.  The  mental  deterioration  is  some- 
times so  great  that  the  patient  has  to  be  sent  to  an  asylum.  But  I 
cannot  help  thinking  that  the  frequency  with  which  well-marked 
mental  disturbances  of  this  kind  occur  is  probably  somewhat  less. 
than  the  statistics  of  the  Clinical  Society  seem  to  show. 


MYXCEDEMA.  307 

In  5  of  my  33  cases  of  adult  myxcedema,  the  patients  were 
mentally  depressed  ;  in  one  case,  a  condition  of  partial  psychical 
blindness  was  present.  One  patient,  who  had,  previously  to  her 
admission  to  hospital,  been  much  depressed,  but  who  presented  no 
suspicious  symptoms  at  the  time  of  her  admission,  jumped  out  of 
the  window  of  the  ward  two  days  after  her  admission  and  killed 
herself.  This  unfortunate  accident  occurred  before  the  patient  had 
been  placed  on  thyroid  treatment. 

It  must  not,  however,  be  supposed  that  slowness  of  thought 
and  mental  deterioration  are  essential  features  of  the  disease.  In 
a  well-marked  case  which  I  saw  with  Dr  Menzies,  and  in  which  a 
complete  cure  has  been  established  under  the  thyroid  treatment, 
the  mental  faculties  of  the  patient  were  quite  keen  and  acute.  It  is, 
too,  important  to  remember  that  in  those  cases  in  which  the  cerebral 
functions  are  profoundly  altered,  the  mental  alteration  is  usually 
the  result  of  functional  derangement  and  not  of  organic  disease. 
The  fact  that  as  the  result  of  thyroid  treatment  in  cases  of 
myxcedema  the  mental  symptoms  may  entirely  clear  off  in  the 
course  of  a  few  days  or  weeks,  and  that  in  cases  of  sporadic 
cretinism  an  undoubted  development  may  occur  in  the  mental 
condition  in  the  course  of  a  few  weeks,  proves  this. 

I  should  also  state  that  in  some  cases  temporary  conditions  of 
garrulousness,  irritability  or  mental  excitement  occur.  But  in  my 
experience  this  is  rare. 

The  condition  of  the  sensory  nerve  apparatus. — Sensory 
symptoms  are  in  most  cases  less  striking  and  important.  Numbness 
in  the  hands  and  feet  is  often  complained  of,  but  objective  disturb- 
ances of  sensation  (either  to  touch,  pain,  heat,  or  cold)  can  rarely 
be  demonstrated.  The  tactile  sensibility  of  the  skin  is  in  some  cases 
delayed  or  diminished  ;  wThether  this  is  due  to  an  alteration  in  the 
sensory  nerve  apparatus  or  merely  to  an  altered  condition  of  the 
skin  is,  I  think,  doubtful ;  both  conditions  probably  account  for 
the  alteration.  Sight  and  hearing  are  in  many  cases  impaired.  In 
one  of  my  cases  the  eyesight  was  so  bad  that  the  patient  could 
scarcely  see  at  night  during  the  winter  months.  In  one  case 
temporary  paralysis  of  the  external  rectus  muscle  and  diplopia 
were  developed  ;  but  whether  this  was  the  result  of  the  disease  or 
merely  an  accidental  complication  I  am  unable  to  say.  Taste  and 
smell  are  in  some  cases  impaired,  though  rarely  in  a  marked 
degree. 

In  13  of  my  33  cases  of  adult  myxcedema,  numbness  of  the 
hands  and  feet  was  complained  of;  in  13  cases  sight  was  impaired  ; 
and  in  1 1  cases  hearing  was  impaired. 


308  DISEASES   OF   THE    BLOOD   GLANDS. 

Headache,  which  is  usually  frontal  though  sometimes  occipital, 
is  not  uncommon  ;  neuralgic  pains  and  cramps  are  occasionally 
experienced  ;  faintness,  giddiness,  tinnitus  aurium  are  in  some  cases 
complained  of. 

Headache  was  complained  of  in  16  of  my  33  cases  of  adult 
myxcedema. 

The  condition  of  the  reflex  nerve  apparatus. — The  reflexes 
do  not  present  any  changes  of  importance ;  they  are  usually 
diminished ;  in  some  cases  the  knee-jerks  are  abolished. 

Temperature. — Increased  susceptibility  to  cold  is  highly  charac- 
teristic. Myxedematous  patients  are  almost  invariably  worse  in 
cold  and  better  in  warm  weather.  One  patient,  for  example,  volun- 
teered the  statement  that  she  felt  quite  a  different  person  in  warm 
weather,  that  in  cold  weather  she  seemed  unable  to  think  or 
exert  herself.  Several  of  my  patients  have  told  me  that  they 
could  not  get  warmed  up  even  if  they  roasted  themselves  before  a 
hot  fire,  that  the  hands  and  feet  were  always  cold  ;  one  patient 
said  she  frequently  felt  as  if  cold  water  were  being  poured  down 
her  back  ;  another  complained  every  now  and  again  of  shivering, 
followed  by  running  at  the  eyes  and  nose  and  debility.  Some 
myxcedematous  patients  dislike  drinking  anything  cold.  Increased 
susceptibility  to  cold  was  present  in  all  of  my  33  cases  of  adult 
myxcedema. 

There  are,  however,  exceptions  to  some  of  these  statements. 
The  husband  of  one  patient,  who,  when  I  first  saw  her,  com- 
plained greatly  of  the  cold,  for  example,  wrote  (and  this,  be  it 
observed,  was  before  the  thyroid  treatment  was  commenced),  "The 
advent  of  frost  caused  her  to  rally  to  such  a  degree  that  she  went 
out,  and  enjoyed  herself  immensely  when  everybody  felt  the 
intense  cold  to  be  slightly  inconvenient."  He  added,  "  In  this 
connection  I  may  mention  that  she  rarely  has  cold  limbs  or  feet 
now.  There  is  a  great  change  for  the  better  in  this  respect."  In 
another  case,  the  patient,  who  first  suffered  from  exophthalmic 
goitre  and  then  from  myxcedema,  stated  that  "  several  times  in 
the  course  of  the  day  a  feeling  of  flushing  and  heat  passed  over" 
her.  In  a  third  case,  the  patient  complained  of  the  frequent  occur- 
rence of  flushing  (burning)  of  the  cheeks. 

The  increased  susceptibility  to  cold  is  not  merely  a  subjective 
symptom,  for  the  temperature,  as  measured  by  the  thermometer,  is 
subnormal  (in  one  of  my  cases,  for  example,  it  was  usually  about 
96.5°  F.),  and  the  diurnal  variations  in  temperature  are  much  less 
marked  than  normal.  The  morning  and  evening  temperatures  are 
in   many  cases  practically  the  same ;    the  diurnal  rises  and   falls 


MYXCEDEMA.  309 

which  occur  in  health  may  be  almost  entirely  absent.  I  have 
noticed,  too,  that  in  many  cases  of  the  disease  the  temperature 
does  not  rise  above  normal  as  the  result  of  conditions  which,  under 
ordinary  circumstances,  would  produce  very  considerable  pyrexia. 
In  connection  with  the  diminished  temperature,  it  is  important  to 
remember  that  in  consequence  of  the  remarkably  dry  condition  of 
the  skin  the  amount  of  heat  which  is  given  off  from  the  surface  of 
the  body  must  be  very  much  less  than  normal.  When  we  take 
these  two  facts  in  association — the  subnormal  temperature  and  the 
diminished  surface  loss — it  is  obvious  that  the  heat  production  in 
cases  of  myxoedema  must  be  much  below  the  normal. 

In  all  of  my  33  cases  of  adult  myxcedema,  the  temperature  was 
subnormal. 

The  condition  of  the  circulatory  system. — The  pulse  is  usually 
slower  than  normal,  and  in  many  cases  soft  and  weak  ;  the  re- 
spirations are  in  some  cases  less  frequent  than  normal. 

The  heart's  action  (impulse  and  sounds)  is  usually  very  feeble  ; 
the  aortic  second  sound  is  not  unfrequently  accentuated.  In 
old  patients,  and  in  the  advanced  stages  of  long  standing  cases,  the 
cardiac  muscle  may  be  degenerated  and  the  arteries  atheromatous. 

This  is  a  very  important  point  so  far  as  treatment  is  concerned  ; 
for,  as  I  shall  presently  point  out,  thyroid  treatment  is  apt  to 
produce  very  marked  depression.  In  those  cases  in  which  there  is 
any  reason  to  suspect  disease  or  degeneration  of  the  heart  or 
arteries,  the  thyroid  treatment  has  to  be  conducted  with  very  great 
care. 

Fainting  occasionally  occurs.  The  patients  usually  complain  of 
shortness  of  breath  on  exertion.  Palpitation  is  sometimes  trouble- 
some ;  one  of  my  patients,  a  medical  man,  stated  that  he  used  to 
wake  with  "  a  tremendous  sensation  of  oppression  in  the  region 
of  the  heart."  Palpitation  on  exertion  was  complained  of  in  9  of 
my  33  cases  of  adult  myxcedema. 

Some  ancsmia  is  usually  present,  but  it  is  rarely  marked.  Both 
the  red  blood  corpuscles  and  the  haemoglobin  are  usually  mode- 
rately diminished  in  number.  The  red  corpuscles  are,  so  far  as 
I  have  observed,  normal  in  size  and  shape  ;  the  white  corpuscles 
are,  in  some  cases,  slightly  in  excess  in  number.  In  the  case  re- 
presented in  Plate  I.  of  my  Atlas  of  Clinical  Medicine,  the  red 
blood  corpuscles  numbered  3,320,000  per  cubic  millimetre,  the 
white  blood  corpuscles  were  slightly,  but  only  slightly,  in  excess, 
and  the  haemoglobin  equalled  70  per  cent.  In  a  second  most 
typical  case  the  red  corpuscles  numbered  3,820,000,  and  the 
haemoglobin  equalled  65  per  cent. 


3IO  DISEASES   OF   THE   BLOOD   GLANDS. 

More  or  less  marked  anaemia  was  present  in  26  of  my  33  cases 
of  adult  myxcedema. 

The  condition  of  the  digestive  apparatus. — The  appetite  is 
usually  much  impaired  ;  dyspepsia  is  not  uncommon.  In  most 
cases  there  is  constipation  ;  in  exceptional  cases  the  patients  suffer 
every  now  and  again  from  attacks  of  diarrhoea  ;  piles  are  occa- 
sionally complained  of.  In  my  33  cases  of  adult  myxcedema,  the 
appetite  was  poor  or  bad  in  29  cases,  and  good  in  3  cases  ;  the 
bowels  were  regular  in  8  cases,  constipated  in  22  cases,  and  loose  in 
3  cases. 

The  condition  of  menstruation :  haemorrhages. — As  I  have 
already  stated,  myxcedema  is  most  usually  developed  in  married 
women  who  have  borne  families  ;  in  some  cases  there  is  amen- 
orrhcea ;  in  others,  menorrhagia.  The  onset  of  the  disease  is,  as 
I  have  already  remarked,  often  preceded  by  menorrhagia.  In 
some  cases,  the  amenorrhoea  is  without  doubt  the  direct  result 
of  the  disease  ;  this  is  proved  by  the  fact  that  in  some  cases  of 
myxcedema  in  which  menstruation  has  been  arrested,  the  men- 
strual flow  is  restored  as  the  result  of  the  thyroid  treatment ; 
in  other  cases,  the  amenorrhcea  may  be  explained  by  the  circum- 
stance that  the  myxcedematous  symptoms  only  become  fully 
developed  after  middle  age,  i.e.,  at  a  time  when  menstruation  would 
naturally  cease.  Myxcedematous  women  who  happen  to  become 
pregnant  (but  this  is  comparatively  speaking  rare)  are  apt  to  suffer 
from  profuse  and  exhausting  haemorrhage  after  delivery.  In  some 
cases,  there  is  a  tendency  to  hcemorrhage  (epistaxis,  bleeding  from 
the  gums,  etc.),  quite  independently  of  pregnancy  and  parturition  ; 
but  in  the  cases  which  have  come  under  my  own  notice  this  ten- 
dency has  very  rarely  indeed  occurred  in  the  later  and  fully 
developed  stages  of  the  disease.  Menorrhagia  is,  however,  in  my 
experience  not  uncommon.  In  the  29  female  cases  of  adult 
myxcedema  which  I  have  observed,  the  menstruation  was  regular 
and  natural  in  2  cases;  arrested  in  19  cases  (in  12  of  these  the 
amenorrhcea  appeared  to  be  due  to  the  occurrence  of  the 
menopause) ;  irregular  in  I  case ;  irregular  and  scanty  in  I 
case  ;  scanty  in  1  case  ;  and  too  profuse  (menorrhagia)  in  5  cases. 
In  3  of  the  12  cases  in  which  the  menstruation  was  arrested 
in  consequence  of  the  menopause,  there  had  previously  been 
menorrhagia. 

The  condition  of  the  urine.— The  urine  is  in  some  cases 
normal,  although  the  amount  of  urea  is  usually  diminished.  In 
other  cases  a  certain  amount  of  albumen  is  present.  This  is  some- 
times doubtless  due  to  associated  cirrhosis  of  the  kidney,  but  in  the 


MYXCEDEMA.  3 1 1 

majority  of  cases  the  albuminous  condition  of  the  urine  appears 
to  be  the  direct  result  of  the  myxedematous  condition.  That  this 
is  so  is  proved  by  the  fact  that  the  albuminuria  may  completely 
disappear  in  the  course  of  a  few  weeks  as  the  result  of  thyroid 
treatment.  In  one  of  my  cases  the  urine  contained  a  distinct 
trace  of  globulin,  but  no  serum  albumen  ;  in  another  case  a  con- 
siderable quantity  of  peptone  was  present  ;  in  one  case  there  was 
a  distinct  trace  of  sugar. 

In  6  out  of  my  33  cases  of  adult  myxcedema,  the  presence  of 
albumen  was  noted  ;  in  4  of  these  cases  the  amount  was  small — 
a  trace  ;  in  2  cases  considerable. 

In  the  cases  tabulated  by  Drs  Hun  and  Prudden,  albumen  was 
absent  in  ninety-one  and  present  in  twenty-two  cases  ;  in  three  of 
the  twenty-one  cases  in  which  albumen  was  present  it  did  not  appear 
in  the  urine  until  late  in  the  course  of  the  disease ;  and  in  five 
of  the  twenty-one  cases  the  albumen  was  not  constantly  present, 
but  only  appeared  from  time  to  time. 

The  relative  frequence  with  which  some  of  the  more  important 
symptoms  occurred  in  my  cases  is  shown  in  Table  8,  pages  312 
and  313. 

Course. — The  course  of  myxoedema  is  usually  slow  and  chronic. 
In  one  case,  the  disease  had  been  in  existence  for  thirty-four  years 
before  the  patient  came  under  my  notice.  The  profound  altera- 
tions which  diminished  or  arrested  thyroid  secretion  produces 
in  the  organs  and  tissues  of  the  body  seem  to  be  functional  in 
character.  The  disease  does  not  kill  as  a  rule  until  it  has  been  in 
existence  for  many  years,  and  even  in  old  people  the  symptoms  of 
the  disease  may  entirely  disappear,  and  the  health  and  activity 
both  of  body  and  mind  be  restored  in  a  very  remarkable  way  under 
a  course  of  thyroid  treatment. 

Death  is  usually  due  to  the  occurrence  of  some  complication, 
such  as  bronchitis,  pneumonia,  influenza,  diarrhoea,  &c. ;  to  cardiac 
degeneration,  an  atheromatous  condition  of  the  arteries  or  the  struc- 
tural changes  associated  therewith  ;  or  to  the  development  of  some 
associated  disease,  such  as  cirrhosis  of  the  kidneys.  In  a  few  cases 
cerebral  haemorrhage  is  the  immediate  cause  of  death.  In  some 
cases,  the  patients  appear  to  die  purely  from  the  exhaustion,  debi- 
lity, and  defective  nutrition  which  the  myxcedematous  condition 
entails  ;  and  particularly  perhaps  from  the  impaired  nutrition  and 
degenerative  changes  in  the  heart  muscle  which  the  myxcede- 
matous condition  and  the  anaemia,  which  is  apt  to  be  associated 
with  it,  occasion. 


312 

Table  8.— 

Showing 

THE 

Frequency 

OF 

THE 

MORE 

and  Sporadic  Cretinism 

i 

y. 

u 
to 

< 

X 

CO 

°       5 

s     -5 
0     — 

"3          -3 

^     r 

.   .    c 
— 1  JJ    u 

i  :;.  _~ 

t.a  B 

cUM    3 

Duration 

when  First 

Seen. 

Apparent 
Cause. 

P 

,|o 

o 

c 

-a  J, 

^  E 
Si  2 
a  ft 

o 

a  w. 

o 

J!  c 

a  a 

rt  v 

— 

X 

■a 
c 

U 

O  j 

S^ 

-2 -a 
c  c 
3  rt 
Z 

X 

a 

0*3 
O 

c 
-a 

^o 

IS 
H 

E73 

c  c 

>> 

CO 

> 

-"  c 

■g.9 

a 
o 

33     . 
,r  J3 

S  rt 
"3  « 

XI 

Myxedematous 
Swelling  of 

a 

3 

O          yT 

>  hi. 

JS_C 
3^ 

a 

c 
d 

X 

Et, 

a 

S 

o 

< 

3 
Ml 
C 

o 

H 

p 

i 

52 

F. 

S.    . 

12  years 

Grief          1 

I 

I 

o 

I 

I 

o 

o 

i 

B.2 

o 

o 

I 

I 

i 

I 

-■ 

59 

M. 

M.   . 

5      » 

0               1 

I 

I 

o 

1 

•> 

? 

9 

i 

G.2 

o 

o 

I 

I 

? 

3 

63 

F. 

W.    6 

20      ,, 

0               1 

I 

I 

o 

I 

I 

I 

i 

G. 

o 

o 

I 

I 

i 

4 

26 

F. 

S.    . 

4      ,, 

0               1 

I 

I 

o 

o 

o 

I 

i 

G. 

o 

o 

I 

I 

i 

5 

41 

F. 

M.       J 

4      ,, 

0               1 

I 

I 

o 

o 

o 

I 

i 

G. 

o 

o 

I 

I 

i 

6 

40 

F. 

M.    . 

2            ), 

(  Mental  \ 
"(  anxiety  1 

I 

I 

I 

o 

o 

? 

i 

G.d3 

o 

I 

I 

I 

i 

: 

42 

F. 

M.    8 

(  A  severe  ) 
(    illness    ) 

I 

I 

o 

I 

o 

I 

i 

B. 

o 

o 

I 

I 

0 

s 

35 

M. 

M.  . 

2          ,, 

O                   3 

I 

I 

o 

? 

7 

o 

o 

i 

9 

o 

o 

I 

I 

i 

9 

IO 

ii 

48 
33 
61 

F. 
F. 
F. 

W.    1 
M.    7 
M.    7 

5       j, 

3   „    { 

3      ,, 

/  Mental  \ 
(_  distress   ) 
Loss  of  bl'd   \ 
and  mental    >    ] 
worry        J 
o                1 

1 
I 

I 

I 
I 
I 

o 
o 

I 

o 

I 
I 

o 

I 
I 

I 

I 
I 

i 
i 
i 

G. 

9 

B. 

I 
I 
o 

I 
I 
o 

I 
I 
S.4 

o 

I 
I 
O 

i 
i 
o 

12 

61 

F. 

M.    2 

8      ,, 

O                     1 

I 

o 

o 

o 

o 

o 

o 

i 

G. 

o 

o 

I 

I 

I 

o 

13 

5° 

F. 

M.  1 

5      3      .» 

O                       ] 

I 

I 

o 

I 

I 

I 

o 

i 

? 

I 

o 

I 

I 

I 

I 

14 

73 

F. 

M.    7 

34      » 

O                       ] 

I 

I 

o 

I 

I 

o 

o 

i 

B.d3 

o 

I 

I 

I 

I 

1 

!5 

5i 

F. 

M.    5 

20      ,, 

o 

I 

I 

o 

o 

o 

o 

o 

i 

G. 

o 

o 

I 

I 

I 

1 

l6 

60 

F. 

M.    j 

2      ,, 

o 

I 

I 

o 

o 

o 

1 

? 

i 

G. 

o 

o 

I 

I 

I 

1 

17 

55 

F. 

S.    . 

.   .   „    { 

Atrophy     -\ 

after         I 

exoph. goitre  ' 

[      I 

I 

o 

o 

o 

I 

? 

i 

G. 

o 

o 

I 

I 

I 

o 

l8 

67 

F. 

M.    « 

4      >, 

o 

[      I 

o 

o 

I 

o 

I 

o 

o 

G. 

o 

o 

o 

o 

o 

o 

19 

40 

F. 

W.    ( 

>       4      » 

o 

I 

i 

o 

o 

o 

o 

o 

I 

G. 

o 

o 

I 

I 

I 

I 

20 

60 

P. 

M. 

>           2         ,, 

o 

r.       I 

i 

o 

I 

I 

0 

o 

1 

G. 

o 

o 

I 

I 

I 

o 

21 

3i 

F. 

M. 

>           3          >, 

o 

I      I 

i 

o 

o 

o 

o 

o 

1 

G. 

o 

o 

I 

I 

I 

22 

60 

F. 

W. 

)       3      ,. 

o 

I      I 

i 

o 

I 

I 

9 

I 

I 

G. 

o 

o 

I 

I 

I 

23 

66 

M. 

M.  . 

•      7      » 

1    Mental  1 
(.    shock    / 

[       I 

i 

o 

o 

I 

9 

? 

I 

G. 

I 

9 

I 

I 

I 

O 

24 

36 

M. 

M.   . 

.      6      „ 

o 

r       I 

i 

o 

o 

o 

o 

I 

I 

G. 

o 

o 

I 

I 

I 

O 

25 

33 

F. 

M.   . 

•       3       >, 

o 

I       I 

i 

o 

o 

o 

I 

I 

I 

G. 

o 

o 

I 

I 

I 

I 

26 

42 

F. 

W. 

^     3    >, 

o 

I       I 

i 

I 

o 

o 

o 

o 

I 

G. 

o 

o 

I 

I 

I 

o 

I 

-7 

5o 

F. 

M. 

3    12    ,, 

o 

I       I 

i 

I 

o 

o 

I 

I 

I 

B. 

o 

o 

o 

S.4 

0 

0 

° 

o 

O 

28 

30 

F. 

M. 

3      4  months 

Grief 

I       I 

i 

I 

I 

I 

I 

o 

I 

B. 

o 

o 

I 

0 

o 

I 

1 

O 

29 

64 

F. 

M.  1 

0     3  years 

?  Influenza 

I       I 

i 

o 

o 

o 

'  1 

o 

I 

G. 

o 

o 

I 

I 

I 

I 

9 

I 

3r 

32 

F. 

S. 

•      4      „ 

o 

I       I 

i 

o 

I 

o 

0 

o 

I 

G. 

o 

o 

I 

I 

o 

I 

" 

o 

31 

41 

F. 

S. 

•     14      » 

?  Inherited 

I       I 

i 

o 

o 

o 

o 

o 

I 

G. 

o 

o 

I 

I 

I 

I 

7 

9 

3= 

32 

F. 

M. 

2       2      ,, 

f     After     )_ 
(  confine't  i 

I       I 

i 

I 

I 

I 

I 

« 

I 

G. 

o 

o 

I 

I 

I 

I 

o 

o 

o 

33 

48 

F. 

S. 

4J  months 

o 

I       I 

i 

o 

o 

o 

I 

1 

o 

? 

o 

o 

o 

o 

o 

o 

o 

0 

o 

34 

14 

F. 

4  years 

o 

I       I 

i 

° 

o 

o 

o 

o 

o 

G. 

o 

o 

I 

T 

I 

o 

o 

o 

I 

3! 

8i 

F. 

•      8      „ 

o 

I       I 

o 

o 

0 

o 

R.1 

G. 

O 

o 

I 

I 

I 

I 

o 

i ' 

I 

3' 

.<". 

F. 

.   '!  From  birth 

o 

I       I 

o 

o 

o 

o 

R. 

G. 

o 

I 

1 

I 

1 

1 

i 

I 

r, 

3 

F. 

2  J  years 

o 

,       9 

G. 

o 

o 

I 

I 

I 

I 

? 

I 

3i 

4 

F. 

•     3*      ,. 

o 

l       I 

o 

o 

R. 

G. 

o 

o 

I 

I 

I 

I 

? 

I 

r 

2^ 

F. 

.   Since  birth 

o 

I       o 

R. 

G. 

o 

o 

I 

'1 

o 

I 

'•' 

o 

4' 

)    36 

F. 

1  rom  birtl 

o 

0        I 

1 

o 

o 

o 

<> 

o 

R. 

G. 

o 

o 

I 

I 

I 

I 

9 

I 

ADDITIONAL  REMARKS. — Case  I.  Formerly  menorrhagia  ;  angina  pectoris.  Case  2.  Right  hemiplegia,  ?from  cerebral 
'  a  '•  4.  Uncle  died  of  myxocdema.  Case  5.  One  cold  winter  felt  better  and  brisker  during  the  cold  weather. 
Case  17.  The  myxcedema  followed  exophthalmic  goitre;  has  frequent  flushings;  a  sister  also  suffered  from 
Case  23.  Trace  of  sugar  in  the  urine.  Case  24.  Frequently  woke  with  feeling  of  terrible  oppression  in  the  region  of 
Marked  mental  depression  ;  jumped  out  of  the  window  and  killed  herself.  Case  30.  Acute  eczema  at  the  commence- 
suffered  from  ulceration  of  stomach.  Case  32.  Considerable  mental  depression.  Case  33.  Considerable  anamiia 
menstruated  regularly. 
*  R.  =rough.  '-'  Ii.  bad  or  poor  ;  C=good.  :!  G.d.  =good,  with  dreams  ;  B.d.  =  bad,  with  dreams.  '  S.  =  slight. 
Glob.  =  globulin.     "  A.*  =amenorrh<ea,  previously  "menorrhagia;  A.  =amenorrhcea  ;  I.  =  irregular ;  S.=scanty; 


important  Symptoms  in  40  Cases  of  Myxcedema 
observed  by  the  author. 


313 


mdition 

of 
hyroid. 

as? \ 

fa 

<-   c 
0  0 

0  ^J= 

><   EL, 

1  I 

.  °    t 

3  .2 

X   «       I 

°  HI 

0    c»l   c 

J  a    Pi 

III 

h        1  Absence  of  Sweating. 
H       1  Subnormal  Tem- 
1      perature. 

|  Anatmia. 
Haemorrhages. 

>. 

0, 
0 

Q 

c* 
'Ho 

0 

0 

%  £ 

a      3 

EL.      Ph 

1     70 

0, 
a. 
< 

B. 

S 

0 

c 

< 

a 

a 
z  0 
.2 '3 

'■3  2 
0  »i 

O 

'v 

X 

0, 

_o 

(V 

p 

c   J2 
v  a 

0 

Oh 

CO 

Anterior  Fontanelle 
Unclosed. 

Milk  Teeth. 

Umbilical  Hernia. 

0          Men.3 

0 

!            C.6 

0 

A.*« 

•i 

I     0 

III 

1      1 

1         Cerebral 

0 

0     60 

B. 

c. 

o 

» 

I       I 

III 

1      1 

j    I       At  last 
1    confinement 

I 

1     60 

B. 

c. 

T." 

A.* 

»» 

I      I 
I       I 

I     0     I 
III 

1      1 
1      1 

1                 0 
1                 0 

0 
0 

0    68 
0     70 

B. 
B. 

Oc.  D. 

0 
;       0 

A. 

» 

I      I 

III 

1      1 

1                0 

0 

?    60 

B. 

C. 

0 

S.8 

l 

I       I 

III 

1      1 

1             Men. 

0 

0    62 

G.2 

R. 

0 

M.s 

» 

I      0 

III 

1      1 

1                0 

0 

0      ? 

B. 

C. 

0 

» 

I       I 

I     I     1 

1      1 

1               0 

0 

1     46 

G. 

C. 

Glob. 

A.* 

» 

I      I 

I    ?    1 

1      1 

1           Men. 

0 

1     60 

B. 

R. 

T. 

M. 

11 

I      0 

III 

1      1 

1              0 

0 

3       60 

B. 

C. 

0 

A.  men.* 

.. 

I       I 

I    ?    I 

1      1 

?              0 

0 

D       72 

B. 

D.« 

0 

A.  men 

>« 

I      I 

I    ?    I 

1      1 

t    /  Men.  before  ) 
{    menopause   J 

I 

J       65 

B. 

C. 

0 

A.  men. 

I       I 

I     0     I 

1      1 

0 

I 

3       64 

B. 

R. 

T. 

A.  men. 

» 

I      I 

I     0     I 

1      1 

0 

I 

58 

B. 

C. 

0 

A.  men. 

I 

t      I 

[      I     I 

1      1 

? 

I       c 

)       76 

B. 

R. 

0 

A.  men. 

[      I 

c       0       I 

1      1      : 

0 

I 

70 

B. 

C. 

0 

A.  men. 

„    < 

5        O 

0     I 

1      1      1 

0 

0      c 

>       72 

B. 

C. 

0 

A.  men. 

,, 

I 

0     I 

1      1      i 

Men. 

0      c 

70 

B. 

C. 

0 

M. 

n 

O 

I      I 

1      1      1 

0 

0      c 

80 

B. 

C. 

0 

A.  men. 

"             ] 

I         1 

I       I 

1      1      1 

0 

0      c 

70 

B. 

C. 

0 

R. 

1 

I        3 

I      I 

1      1      1 

0 

0 

68 

B. 

C. 

1 

A.  men. 

.,                 3 

O        1 

0      I 

Oil 

0 

0      I 

60 

B. 

D. 

0 

II                  I 

I         3 

0      I 

1      1      c 

0 

I      I 

72 

B. 

R. 

1 

L          1 

I         C 

0     I 

iii 

Men. 

0      0 

63 

F. 

R. 

0 

M. 

L         1 

O         I 

0      I 

iii 

0 

0     0 

60 

B. 

C. 

0 

A. 

' 

I         I 

I       I 

iii 

Men. 

0     0 

72 

B. 

c. 

0 

A.* 

,         1 

I         I 

0      I 

1      1      ? 

0 

0     0 

72 

B. 

c. 

0 

A. 

,         1 

I         I 

I       I 

1      1      ? 

0 

0     0 

66 

B. 

c. 

0 

A.  men. 

,         1 

I         I 

0      I 

iii 

0 

0     0 

44 

B. 

R. 

0 

I.  S.8 

,         1 

I         I 

0      I 

1      1      1 

Men. 

0     0 

B. 

C. 

0 

M. 

.. 

,         1 

I         O 

0      I 

1      1      1 

0 

0      0 

50 

G. 

C. 

0 

R. 

.. 

,         1 

I         I 

I      I 

i      1      1 

0 

I      I 

100 

B. 

C. 

0 

A.  men. 

1         ° 

I         I 

I      I 

1      1      1 

0 

0     0 

56 

G. 

C. 

0 

N.  M.8 

7t.  In. 

4     2i 

G. 

G. 

0 

P.9     0 

,         1 

I         I 

I      I 

1      1 

0 

0     0 

So 

B. 

C. 

0 

2    ioi 

S. 

G. 

0 

P.       1 

,         1 

O         I 

I      I 

1      0 

0 

0     0 

72 

G. 

C. 

0 

2     4I 

Nil 

Nil 

1 

P.       1 

0 

O         I 

0      0    c 

>      1      1 

0 

0     0 

96 

B. 

C. 

2     2J 

Nil 

Nil 

1 

Vone    1 

1 
0 

I         I 
O         I 

I      I    ] 
I      I    ] 

1      1 
1 

0 

0     0 

80 

G. 
B. 

c. 
c. 

0 
0 

2     3 
2     6 

Very 
little 
G. 

Very- 
little 
Nil 

1      . 
1      i 

Some    1 
Some    1 

1 

O         X 

I      II 

1      0 

° 

0      0 

B. 

R. 

0 

R. 

Very 

light 

Little 

0     I 

iome    0 

a  CcLnUrZJ'  ^,enM:.l:ua,ted  only  once  since  disease  began  twenty  years  ago;  marked  atheroma  of  superficial  vessels. 
h?naWPIobre      r  rair r^u,rS,tatlon;     Case  10.    Frequent  shivering  attacks.     Case  n.    Marked  mental  depression, 

earf     ell    "     W        ,  ^    ?T  beCamu   darker  during  the  disease.     Case  20.    Intercurrent  paralysis  of  external  rectus. 

of  the  dfsease5'-  W  H  TT  tf-  me"°"haK la"  ^Case  27-  Arnenorrhoea  for  three  years  ;  previously  menorrhagia.  Case  28. 
mit «  "re^rllti da,'y  flushlnSs  of  ^eks.  Case  31.  Mother  died  of  myxcedema  ;  brother  has  a  full  heavy  face  ;  for  years 
mitral  regurgitation.     Case  34.  Juvenile  myxcedema.     Case  36.  A  most  extreme  case.     Case  40.  Since  the  age  of  25  has 

e^  a-nfm\I;o=rrnhe^rHr!,agfia-     6  C'  =cons{iPation  5  R-  =regular  ;  D.  =  diarrhcea  ;  Oc.D.  =  occasional  diarrhoea.     "  T.  =  trace  ; 
en. -arnenorrhoea  due  to  menopause  ;  I.  S.  =  Irregular  and  scanty  ;  N.  M.  =  never  menstruated.     "  P.  =  present. 


314  diseases  oe  the  blood  glands. 

Diagnosis. 

The  diagnosis  of  typical  cases  of  myxcedema  presents  no  diffi- 
cult}'. In  fully  developed  cases  {full-blown  cases,  as  I  am  in  the 
habit  of  terming  them),  the  facial  appearance  of  the  patient  is  so 
striking  that  the  disease  can  be  recognised  at  the  first  glance  by 
any  one  who  has  seen  cases  before.  The  remarkable  similarity  in 
physiognomy  which  different  cases  of  myxcedema  present,  and  the 
facility  with  which  the  disease  can  in  many  cases  be  recognised,  is 
well  shown  by  the  following  facts  : — In  one  of  my  cases,  my  son,  a 
second  year's  medical  student  who  had  never  seen  a  case  of  myxce- 
dema, at  once  recognised  the  disease  when  I  asked  him  what  it 
was,  without  having  told  him  that  there  was  any  case  of  myxce- 
dema in  the  hospital,  or  given  him  any  hint  as  to  the  nature  of 
the  disease  with  which  the  patient  was  affected.  He  was  able  to 
recognise  the  disease  from  the  close  resemblance  to  the  plates 
in  my  Atlas  of  Clinical  Medicine.  In  another  case,  the  appear- 
ance of  the  patient  was  so  typical  and  characteristic  that  while  she 
was  standing  at  the  end  of  a  long  passage  (away  from  me  at  a 
distance  of  60  feet)  I  said  to  my  assistant,  Dr  Douglas,  "  That  old 
lady  looks  as  if  she  had  myxcedema."  After  I  had  examined  and 
prescribed  for  her  daughter,  I  questioned  her,  and  found  that  my 
suspicion  was  perfectly  correct. 

The  symptoms  of  which  the  patient  complains,  and  the  physi- 
cal alterations  which  are  produced  in  the  body  as  a  whole,  and  in 
the  skin  and  its  appendages  in  particular,  are  highly  characteristic. 
Further,  the  diagnosis  is  confirmed  by  the  absence  of  disease  in 
any  of  the  organs  (other  than  the  thyroid  gland)  capable  of  ade- 
quately and  satisfactorily  accounting  for  the  condition — in  par- 
ticular, the  absence  of  organic  kidney  disease.  It  must,  however, 
be  remembered  that  in  some  cases  of  myxcedema  there  is  temporary 
albuminuria,  and  that  in  other  cases — I  refer  more  particularly  to 
long-standing  cases  in  old  people— the  disease  is  associated  with 
cirrhosis  of  the  kidney. 

The  most  important  symptoms  and  signs  for  the  purposes  of 
diagnosis  are : — The  general  increase  in  bulk;  the  broad  ("moon- 
shaped  "),  swollen  condition  of  the  face,  the  swelling  of  the  eyelids, 
lips,  etc.  ;  the  dingy  yellow  tint  of  the  skin  of  the  face  ;  the  drooping 
of  the  upper  eyelids,  and  the  compensatory  elevation  of  the  eye- 
brows ;  the  pink  blush  on  the  check;  the  large  broad  ("spade- 
shaped  ")  hands,  and  the  short  broad  feet  ;  the  solid  character  of 
the  oedema  ;  the  supraclavicular  swellings  ;  the  harsh,  dry  condition 
of  the  skin  ;  the  absence  of  sweating  ;  the  subnormal  temperature  ; 


MYXGEDEMA.  3 1 5 

the  increased  sensibility  to  cold  ;  the  dry,  ragged,  brittle  con- 
dition of  the  hair  ;  the  loss  of  hair  on  the  scalp,  eyebrows,  eyelids, 
etc. ;  the  encrusted  condition  of  the  scalp  ;  the  muscular  feebleness; 
the  slow  monotonous  speech  ;  the  thick,  "  leathery "  character  of 
the  tone  of  the  voice  ;  and  the  remarkable  slowness  with  which  the 
act  of  thinking  and,  indeed,  all  the  higher  cerebral  functions  are 
carried  out. 

In  the  slighter  cases  in  which  the  facial  and  other  alterations 
are  less  characteristic  and  the  symptoms  less  marked,  the  more 
important  diagnostic  features  are  : — The  lassitude,  debility  and 
muscular  feebleness  for  which  there  is  no  apparent  cause  ;  the  some- 
what "  full  "  appearance  of  the  face  ;  a  tendency  to  increased  bulk 
of  the  body  as  a  whole  ;  the  yellow  colour  of  the  skin  of  the  face ; 
the  dryness  of  the  skin  ;  the  diminution  of  the  secretion  of  sweat ; 
the  subnormal  temperature  ;  the  increased  sensibility  to  cold  ;  the 
thin,  harsh,  dry  condition  of  the  hair  (though  this  is  not  always 
present);  and  the  slowness  and  thickness  of  articulation. 

In  doubtful  cases  the  effect  of  a  course  of  thyroid  treatment  is 
of  the  greatest  diagnostic  value.  Case  XXXIII.  is  an  excellent 
illustration  in  point. 

The  differential  diagnosis  of  myxcedema  and  Bright's 
disease. — Before  the  clinical  features  of  myxcedema  were  clearly 
differentiated  and  recognised,  the  disease  used  frequently  to  be 
mistaken  for  Bright's  disease.  The  same  mistake  in  diagnosis  is 
still  occasionally  made.  The  swollen  condition  of  the  face  and 
especially  the  baggy  dropsical  swellings  of  the  lower  lids  and  the 
swollen  (cedematous)  condition  of  the  limbs  and  trunk  are  at  first 
sight — and  especially  in  cases  in  which  there  is  no  cardiac  lesion  to 
account  for  the  cedema — suggestive  of  kidney  disease.  Further, 
it  must  be  remembered  that  in  some  cases  of  myxcedema  the  urine 
contains  albumen.  It  is  easy,  therefore,  to  see  how  this  mistake  in 
diagnosis  may  arise. 

The  distinction  between  myxcedema  and  Bright's  disease  must 
be  based  upon  the  condition  of  the  urine,  the  facial  appearance, 
the  peculiar  character  of  the  cedema,  and  the  presence  of  other 
symptoms  indicative  of  the  disease,  especially  the  dry  condition 
of  the  skin,  the  increased  sensibility  to  cold,  the  thickness  of 
speech,  etc. 

The  pink  blush  on  the  cheek  is  highly  characteristic  of  myxce- 
dema. The  solid  character  of  the  cedema  is  another  point  of  great 
diagnostic  value  ;  but  in  this  connection  it  is  necessary  to  remember 
that  in  some  cases  of  myxcedema  ordinary  dropsical  swelling  which 
pits  on  pressure  is  present  in  the  feet. 


316  DISEASES   OF   THE   BLOOD   GLANDS. 

In  those  cases  of  myxcedema  in  which  the  urine  is  free  from 
albumen,  an  examination  of  the  urine  at  once  shows  that  the  case 
is  not  Bright's  disease;  but,  as  I  have  already  stated,  in  a  con- 
siderable proportion  of  cases  of  myxcedema  albuminuria  is  present. 
It  is  in  these  cases  that  the  chief  difficulty  in  diagnosis  occurs,  and 
it  must  be  remembered  that  the  two  conditions  (myxcedema  and 
cirrhosis  of  the  kidney)  may  be  combined.  This,  however,  is,  so 
far  as  my  experience  enables  me  to  judge,  rare,  except  in  the 
terminal  stages  of  long  continued  cases  in  old  people.  In  the  great 
majority  of  cases  of  myxcedema  in  which  the  urine  contains  albumen, 
the  albuminuria  is  merely  functional  and  temporary;  it  may  only 
be  present  after  meals,  and  it  disappears  as  the  myxedematous 
symptoms  are  removed  under  a  course  of  thyroid  treatment.  In 
cases  of  this  kind  (cases  of  myxcedema  complicated  with  functional 
albuminuria),  the  amount  of  albumen  is  rarely  considerable  and  the 
urine  does  not  as  a  rule  contain  casts.  The  presence  or  absence  of 
tube  casts,  then,  is  one  of  the  most  important  points  in  those  cases 
in  which  there  is  difficulty  and  doubt.  In  some  cases,  a  positive 
diagnosis  can  only  be  made  by  watching  the  effects  of  thyroid 
treatment.  In  those  cases  in  which  the  albumen  is  merely  temporary 
and  functional — the  result  of  the  myxcedematous  condition — it 
disappears  under  treatment ;  whereas,  in  those  cases  in  which  it  is 
due  to  Bright's  disease  it  remains. 

It  is  unnecessary  to  refer  in  detail  to  the  many  other  points  of 
distinction  (condition  of  the  skin,  hair,  voice,  articulation,  etc.). 

The  differential  diagnosis  of  myxcedema  and  acromegaly  is 
easy.  Acromegaly  usually  develops  during  early  adult  life,  most 
frequently  between  the  ages  of  18  and  27,  and  seems  to  be  equally 
common  in  the  two  sexes  ;  while  myxcedema  is  chiefly  met  with  in 
middle-aged  and  old  women.  In  acromegaly,  the  face  is  oval  and 
elongated  in  its  lower  part  ;  whereas  in  myxcedema  it  is  notably 
rounded  ("  moon-shaped  ").  The  pink  blush  on  the  cheeks  which  is 
so  characteristic  of  myxcedema  (though  not  invariably  present)  is 
not  seen  in  acromegaly.  The  facial  expression  in  the  two  diseases 
is  quite  different.  The  thick  monotonous  speech  of  myxcedema  is 
not  met  with  in  cases  of  acromegaly.  In  acromegaly,  the  skin 
is  moist  and  the  electrical  resistance  diminished ;  whereas,  in 
myxcedema,  the  skin  is  harsh  and  dry  and  the  electrical  resistance 
markedly  increased.  In  acromegaly,  there  is  an  increased  growth 
of  hair  ;  whereas,  in  myxcedema,  atrophy  of  the  hair  and,  in 
advanced  cases,  baldness  of  the  scalp  are  highly  characteristic 
features.  In  acromegaly,  the  enlargement  chiefly  affects  the  ex- 
tremities ;  whereas,   in   myxcedema,    it    involves   the    whole    body. 


MYX  (EDEMA.  317 

In  acromegaly,  the  bones,  especially  the  short  bones,  are  notably 
increased  in  size  ;  whereas,  in  myxcedema,  the  increased  bulk  of 
the  body  is  entirely  due  to  a  solid  oedema  of  the  soft  parts.  Bilateral 
temporal  hemianopsia,  which  is  such  a  frequent  and  characteristic 
symptom  of  acromegaly,  does  not  occur  in  myxcedema. 

Prognosis. 

Within  the  past  six  or  seven  years  the  prognosis  of  myxcedema 
has  completely  changed.  When  I  wrote  the  article  on  myxcedema 
in  my  Atlas  of  Clinical  Medicine,  published  in  May  1891,  I  stated 
that,  so  far  as  our  present  knowledge  enables  us  to  judge,  myxcedema 
is  (with  very  rare  exceptions)  incurable.  The  exact  reverse  is  now 
the  case.  Thanks  to  the  thyroid  treatment,  the  prognosis  is  now 
invariably  favourable,  provided  always  that  the  patient  is  not  too 
old,  and  that  there  are  no  grave  complications  such  as  a  diseased  or 
degenerated  condition  of  the  heart,  atheroma,  kidney  disease,  etc. 

By  the  administration  of  thyroid  extract  the  myxcedematous 
symptoms  can  in  the  great  majority  of  cases  be  removed  in  the 
course  of  a  short  time ;  and  after  the  removal  of  the  myxcedematous 
condition,  the  patient  can  be  kept  in  good  health  by  the  systematic 
and  regular  administration  of  thyroid  extract.  Even  in  those  cases 
in  which  the  patient  is  old  and  in  which  the  heart  and  arteries  are 
degenerated  or  diseased,  a  carefully  conducted  course  of  thyroid 
treatment  may  produce  the  most  remarkable  improvement.  In  the 
case  which  is  represented  in  Plate  I.,  Atlas  of  Clinical  Medicine 
(see  Case  III.),  the  patient  was  66  years  of  age  when  the  treatment 
was  commenced,  and  she  looked  older  than  her  years.  The  disease 
was  of  twenty-four  years'  duration  ;  the  patient  was  extremely 
debilitated,  the  scalp  was  almost  entirely  bald,  the  arteries  were 
atheromatous,  and  the  heart  exceedingly  feeble — in  short,  the  case 
was  a  very  aggravated  example  of  the  disease  in  an  old  woman 
with  a  weak  heart  and  degenerated  arteries.  Now,  at  the  end  of 
six  years,  she  looks  at  least  ten  years  younger  than  her  age ; 
the  myxcedematous  symptoms  have  entirely  disappeared,  she  has 
regained  her  mental  activity,  her  articulation  is  sharp,  she  is  able 
to  attend  to  her  household  duties,  her  head  is  covered  with  a  thick 
growth  of  long  black  hair,  which  is  no  doubt  one  of  the  reasons 
why  she  looks  much  younger  than  her  actual  age.  Further,  since 
her  recovery,  she  has  passed  through  a  severe  attack  of  influenza 
complicated  with  pneumonia,  the  attack  being  so  severe  that  she 
was  unconscious  for  days.  No  more  remarkable  illustration  than 
this    could    be   wished    of  the    extraordinary   benefit    which   may 


3 18  DISEASES   OF   THE    BLOOD   GLANDS. 

be  obtained,  even  in  very  advanced  and  apparently  unfavourable 
cases,  by  a  carefully  conducted  course  of  thyroid  treatment. 

In  connection  with  the  prognosis  in  cases  of  myxcedema,  I  can- 
not too  forcibly  emphasise  the  fact  that  a  course  of  thyroid  treatment 
produces  a  very  depressing  effect  upon  the  heart,  and  that  in  those 
cases  in  which  the  heart  is  degenerated  or  diseased,  in  which  the 
patient  is  very  old  or  debilitated,  and  in  which  the  arteries  are 
atheromatous,  there  is  an  undoubted  risk  of  fatal  syncope  unless 
rigid  precautions  are  taken  to  prevent  cardiac  failure  during  the 
early  stages  of  the  thyroid  treatment. 

SPORADIC  CRETINISM. 

Before  leaving  the  clinical  history  of  myxcedema  it  may  perhaps 
be  well  to  refer  in  more  detail  to  the  interesting  condition  which  is 
termed  sporadic  cretinism.  We  now  know  that  this  disease  is  much 
more  common  than  was  supposed  a  few  years  ago.  Since  the  in- 
troduction of  the  thyroid  treatment  a  large  number  of  cases  have 
been  reported,  more  especially  in  this  country.  Sporadic  cretinism 
is  merely  the  infantile  form  of  myxcedema ;  the  symptoms  of 
myxcedema  and  sporadic  cretinism  are  in  many  respects  the  same. 
Any  differences  which  exist  between  the  two  affections,  or  which  at 
first  sight  and  on  superficial  observation  appear  to  exist  between 
them,  are  amply  accounted  for  by  the  different  ages  at  which  the 
disease  is  developed.  Myxcedema  usually  attacks  the  fully  de- 
veloped and  adult  organism,  while  sporadic  cretinism  attacks  the 
non-developed  and  infantile  organism.  The  profound  disturbances 
in  nutrition  which  result  are  attended  with  the  arrest  or  non- 
development  both  of  the  body  and  mind. 

Sporadic  cretinism,  like  myxcedema  in  the  adult,  is  due  to 
diminution  or  abolition  of  the  function  of  the  thyroid  gland.  In 
some  cases  of  sporadic  cretinism  the  thyroid  gland  seems  to  be 
congenitally  absent  ;  in  others,  to  be  atrophied  as  the  result  of 
disease  originating  in  early  extra-uterine,  or  perhaps  in  some  cases 
during  intra-uterine  life. 

Sporadic  cretinism,  like  the  ordinary  form  of  myxcedema,  is 
much  more  common  in  females  than  in  males.  All  of  the  six  cases 
which  have  come  under  my  own  notice  were  females. 

The  symptoms  characteristic  of  sporadic  cretinism  usually  be- 
come apparent  before  the  third  or  fourth  year,  sometimes  during 
the  first  k\v  months  after  birth,  not  unfrequently  during  the  period 
of  first  dentition.  In  some  cases,  the  symptoms  of  the  disease  are 
first  noticed  after  recovery  from  an  acute  febrile  disease,  such  as 


MYXCEDEMA.  319 

measles  or  scarlet  fever;  in  rare  instances,  the  disease  appears  to 
develop  after  an  injur)-.  In  a  few  of  the  reported  cases,  the  mother 
is  stated  to  have  received  a  fright  during  pregnancy  ;  in  a  small 
proportion  of  cases,  the  birth  of  the  child  was  attended  with 
unusual  difficulty,  or  the  mother's  health  was  seriously  disturbed  by 
sickness,  traumatic  injury,  etc.,  during  pregnancy.  It  has  also 
been  suggested  that  conception  when  one  of  the  parents  was  in  a 
state  of  intoxication  may  be  a  cause  of  the  disease ;  but  this 
appears  to  be  quite  exceptional.  In  a  considerable  number  of 
recorded  cases,  the  near  relatives  of  the  parents  were  tubercular  or 
neurotic. 

From  this  statement,  it  will  be  apparent  that  in  some  cases  of 
sporadic  cretinism  the  absence  or  atrophy  of  the  thyroid  gland  is 
apparently  due  to  arrested  development  or  pathological  conditions 
occurring  during  intra-uterine  life  ;  in  others,  to  the  result  of  patho- 
logical conditions  during  the  first  few  months  or  years  of  extra- 
uterine life.  But  in  sporadic  cretinism,  as  in  the  adult  form  of 
myxcedema,  further  information  is  required  as  to  the  conditions 
which  cause,  or  predispose  to  the  production  of,  the  thyroid  lesion. 

Patients  affected  with  sporadic  cretinism,  like  patients  affected 
with  myxcedema,  usually  bear  a  remarkable  resemblance  to  one 
another.  It  must,  however,  be  remembered  that  the  severity  of  the 
disease  varies  very  greatly  in  different  cases. 

In  typical  and  fully  developed  cases  of  sporadic  cretinism,  the 
appearance  is  very  striking.  The  body  is  markedly  stunted, 
dwarfed,  heavy-looking,  and  podgy.  At  thirty-six  years  of  age, 
the  patient  may  only  measure  three  feet  in  height  (see  Case  XL.). 
The  mental  development  is  more  or  less,  and  in  many  cases  almost 
entirely,  arrested.  The  patient,  though  in  years  an  adult,  is,  in 
respect  to  stature,  mental  condition,  and  sexual  development,  a 
mere  child.  The  anterior  fontanelle  often  remains  unclosed.  The 
milk  teeth,  which  are  usually  very  late  in  being  cut  and  which  are 
generally  irregular,  worn  down,  or  carious,  may  persist  even  after 
adult  age  is  reached.  The  face,  abdomen,  limbs  and  body  generally 
are  swollen,  and  the  tissues  are  infiltrated  with  a  solid  oedema 
which  does  not  pit  on  pressure.  The  facial  appearance  is  highly 
characteristic  and  often  extremely  ugly.  The  expression  is  heavy 
and  apathetic.  The  skin  in  some  cases  has  a  dingy  hue  ;  about  the 
eyelids  it  is  usually  wax-like  and  translucent.  The  face  is  very 
broad  ("  moon-shaped  ")  and  coarse-looking  ;  the  eyes  are  set  wide 
apart ;  the  forehead  is  usually  low  and  narrow  ;  the  cheeks  are  fat, 
pendulous  and  baggy  ("jowl-like") ;  the  nose  flat  and  pug-shaped  ; 
the    eyelids    swollen  ;    chronic    inflammation    of  the    lids    (ciliary 


320  DISEASES   OF   THE   BLOOD    GLANDS. 

blepharitis)  is  sometimes  present ;  the  mouth  is  unusually  large,  the 
lips  thick  and  swollen,  the  lower  lip  often  everted  and  in  many 
cases  blue  ;  the  tongue  is  almost  always  very  large  and  thick,  and, 
in  some  cases,  is  kept  constantly  protruded  between  the  teeth.  The 
pink  blush  on  the  cheeks  which  is  such  a  striking  feature  in  cases 
of  myxoedema  is  not  usually  present  in  cases  of  sporadic  cretinism. 
A  fine  growth  of  downy  hair  in  some  cases  covers  the  forehead. 
The  head  is  usually  large  in  proportion  to  the  size  of  the  body.  As 
I  have  already  stated,  the  anterior  fontanelle  often  remains  un- 
closed, even  after  the  patient  has  attained  the  adult  age.  The  ears 
are  in  many  cases  large,  pale,  and  swollen-looking.  The  hair,  which 
is  in  most  cases  fairly  abundant,  more  especially  on  the  back  and 
sides  of  the  head,  is  usually  straight,  dry,  and  coarse;  in  some  cases, 
it  looks  like  horse-hair.  During  infancy,  a  scaly  or  eczematous 
eruption  is  very  generally  present  on  the  scalp;  and  this  dry,  rough, 
scaly,  and  encrusted  condition  of  the  scalp  persists,  in  many  cases, 
throughout  life.  The  neck  is  unusually  short  and  thick;  a  depression 
can  often  be  felt  in  the  position  of  the  thyroid  gland.  Elastic 
swellings,  which  in  some  cases  attain  to  such  large  size  as  to  be 
actual  deformities,  are  in  well-marked  cases  almost  invariably  pre- 
sent in  the  supraclavicular  regions,  sometimes  in  the  axillae  or  else- 
where. A  subcutaneous  thickening,  which  is  probably  due  to 
deposits  of  fat,  is  in  some  cases  present  in  the  upper  dorsal  region 
between  the  scapulae.  A  fine  growth  of  hair  is  often  seen  in  this 
situation.  Enlarged  veins  are  frequently  present  over  the  upper 
part  of  the  chest  and  limbs  and  venous  mottling  of  the  limbs  is  not 
uncommon.  The  abdomen  is  usually  enlarged,  often  enormously 
so  ;  an  umbilical  hernia  is  present  in  a  large  proportion  of  cases  ; 
it  is  generally  of  small  size,  but  this  is  not  always  the  case.  In 
many  cases,  the  belly  is  protruded  and  pendulous,  while  the  back  is 
arched.  The  limbs  are  short  and  broad,  the  lower  limbs  often  curved 
and  apparently  rickety.  The  hands  and  feet  are  broad,  thick,  and 
swollen-looking  ("spade-like");  the  forearms  are  in  many  cases 
remarkably  broad  and  thick  ;  the  feet  and  hands  are  usually  cold, 
and  often  somewhat  purple-coloured.  The  skin  of  the  face,  neck, 
and  abdomen  may  be  fine  and  wax-like,  but  over  the  limbs  and  back 
it  is  usually  rough,  harsh,  and  dry.  The  secretion  of  sweat  is  in 
almost  all  cases  greatly  diminished  or  entirely  abolished.  Moles, 
warts,  and  naevi  are  in  some  cases  present.  The  voice  is  usually 
rough,  hoarse,  and  harsh,  sometimes  squeaky.  The  temperature  is 
usually  subnormal  ;  patients  affected  with  sporadic  cretinism  are, 
with  rare  exceptions,  extremely  susceptible  to  cold  ;  they  like  to  bask- 
in  the  sun  or  roast  themselves  before  a  hot  fire  ;  they  are  usually 


MYXCEDEMA.  321 

much  more  active  and  lively  in  warm  than  in  cold  weather.  The  gait 
is  clumsy  and  waddling ;  in  very  extreme  cases  the  patient  may  be 
unable  to  stand  or  walk.  The  back  is  often  curved,  and  this  deformity 
is  apt  to  become  more  marked  (apparent)  after  a  course  of  thyroid 
treatment.  The  subjects  of  sporadic  cretinism  show  a  singular  re- 
pugnance to  exertion  both  of  body  and  mind.  In  many  instances 
they  will  sit  perfectly  still  in  one  position  for  hours  together,  without 
speaking  or  apparently  taking  any  notice  of  their  surroundings,  and 
yet  perfectly  happy  and  contented.  They  are  usually  of  a  placid 
and  affectionate  disposition  and  generally  very  unemotional  ;  they 
seldom  cry  and  rarely  shed  tears.  They  are  generally  cheerful  and 
easily  amused,  and  are  usually  fond  of  playing  with  other  children, 
animals  and  toys.  Unless  the  case  is  a  very  aggravated  one,  they 
are  generally  cleanly  in  their  habits,  modest  in  their  demeanour 
and,  considering  the  low  state  of  mental  development,  singularly 
careful  of  allowing  themselves  to  be  exposed.  They  usually  sleep 
well,  sometimes  far  too  well. 

The  degree  of  mental  development  varies  very  greatly  in  differ- 
ent cases.  Some  are  little  better  than  idiots,  unable  to  utter  any 
intelligible  speech  sounds,  unable  to  dress,  feed  themselves,  etc. 
Others,  though  twenty-five  or  thirty  years  of  age,  resemble,  as  regards 
their  mental  development,  a  dull  child  of  four  or  five.  In  very 
slight  cases,  the  mental  development  may  be  comparatively  little 
affected.  Between  the  two  extremes,  all  degrees  of  difference  in 
the  mental  development  are  met  with. 

A  notable  and  characteristic  feature  of  the  disease  in  the  great 
majority  of  typical  cases  is  the  arrested  development  of  the 
sexual  organs  ;  even  at  twenty-five  or  thirty  there  are  no  hairs  on 
the  pubes  or  axillae  ;  the  testicles,  ovaries,  and  uterus  are  in  most 
cases  entirely  undeveloped.  As  a  rule,  the  menstrual  function  is 
not  established  even  when  the  patient  is  twenty-five  or  thirty  years 
of  age,  but  exceptions  to  this  statement  occasionally  occur.  In  one 
well-marked  case  which  came  under  my  observation  a  few  years 
ago,  the  patient,  who  was  thirty-six  years  of  age,  and  only  thirty- 
six  inches  in  height,  menstruated  regularly  (Case  XL.),  but  this 
is  quite  exceptional ;  indeed  I  know  of  no  other  well-marked  case 
of  sporadic  cretinism  in  which  the  menstrual  function  was  estab- 
lished. 

The  appetite  is  in  most  cases  moderate  or  capricious,  the  breath 
often  foul  ;  flatulence  is  common  ;  constipation  is  usually  a  very 
prominent  symptom,  but  in  some  cases  diarrhoea  is  readily  produced 
by  slight  dietetic  errors. 

A  slight  degree  of  enlargement  of  the  lymphatic  glands  in  the 

x 


322  DISEASES   OF   THE   BLOOD   GLANDS. 

neck  and  axillae  is  not  uncommon,  but  the  internal  organs  (with  the 
exception  of  the  thyroid)  are  usually  healthy.  In  some  cases,  the 
urine  deposits  a  considerable  quantity  of  mucus. 

Diagnosis. 

In  typical  and  well-developed  cases  of  sporadic  cretinism,  the 
diagnosis  presents  no  difficulty.  The  marked  arrest  in  the  physical 
and  mental  development,  the  peculiar  and  highly  characteristic 
facial  physiognomy,  the  earthy  colour  of  the  complexion,  the  thick- 
ness of  the  neck,  the  depression  in  the  position  of  the  thyroid 
gland,  the  supraclavicular  fatty  swellings,  the  large  swollen  abdomen, 
the  umbilical  hernia,  the  thickness  and  shortness  of  the  limbs  with 
the  curvature  of  the  lower  limbs,  the  short  broad  swollen  hands  and 
small  broad  swollen  feet,  the  rough  harsh  character  of  the  voice,  the 
dry  harsh  condition  of  the  skin,  the  absence  of  sweating,  the  sub- 
normal temperature,  the  marked  susceptibility  to  cold  and  the  love 
of  warmth,  the  repugnance  to  exertion,  the  marked  torpidity  both 
of  body  and  mind,  the  arrested  sexual  development,  and  the  solid 
cedema  which  does  not  pit  on  pressure,  form  a  clinical  picture  which 
it  is  impossible  to  mistake. 

In  slight  cases,  the  retarded  development  of  body,  the  retarded 
mental  development  (though  in  many  cases  this  is  by  no  means 
great),  the  dry  condition  of  the  skin  and  hair,  the  absence  of  sweat- 
ing, the  swollen  condition  of  the  eyelids,  the  large  mouth,  the  large 
tongue,  the  large  broad  hands  and  feet,  the  subnormal  temperature 
and  the  hyper-sensibility  to  cold,  are  the  most  important  diagnostic 
points. 

Prognosis. 

As  yet  it  is  hardly  possible  to  make  any  definite  statement  with 
regard  to  the  ultimate  effects  which  thyroid  treatment  may  produce 
in  respect  to  the  bodily  and  mental  development  in  cases  of  sporadic 
cretinism.  The  length  of  time  which  has  as  yet  elapsed  since  the 
introduction  of  the  thyroid  treatment  is  not  sufficient  to  allow  of 
any  more  definite  statement.  Much,  no  doubt,  will  depend  upon 
the  age  of  the  patient  when  the  treatment  is  commenced,  and  upon 
the  severity  of  the  case.  In  slight  cases,  and  in  cases  in  which  the 
treatment  is  commenced  at  an  early  stage  of  the  disease,  there  is 
every  reason  to  expect  marked  improvement ;  the  effects  which  are 
produced  by  the  thyroid  treatment  in  two  or  three  years  are  most 
remarkable.  In  cases  of  this  kind,  very  considerable  development, 
possibly  the  full  development  of  body  and  mind,  may  ultimately  be 
attained.     But  in  severe  cases,  in  which  the  disease  is  of  long  dura- 


MYXCEDEMA.  323 

tion  (as  in   Case  XXXVI.),  the  degree  of  improvement  which  can 
be  produced  will  probably  be  small. 

These  conclusions  practically  correspond  to  those  arrived  at  by 
Dr  John  Thomson.  In  a  thoughtful  paper  published  in  the  "  British 
Medical  Journal,"  12th  September  1896,  he  says: — 

"  One  of  the  next  things  wanted  in  our  study  of  the  thyroid  treatment  of 
cretinism  is  a  clearer  idea  of  the  amount  and  exact  nature  of  the  improvement 
to  be  hoped  for.  Now,  the  improvement  of  cretins  under  thyroid  is  a  much  less 
simple  thing  than  that  of  ordinary  myxcedematous  adults.  In  cretins,  the  treat- 
ment not  only  clears  away  the  characteristic  deformity  and  dulness,  but  also  lets 
loose  on  the  patient  some  at  least  of  the  natural  impulses  of  growth  which  were 
in  abeyance  in  his  former  thyroidless  condition.  This  latent  capability  of  react- 
ing to  thyroid  treatment  by  a  renewed  growth  and  development  seems  to  be 
present  in  all  cretins,  but  its  degree  varies  enormously,  and  is  apparently  in  direct 
proportion  to  the  youth  of  the  patient  when  the  treatment  is  first  begun.  It 
is  very  strong  in  children,  less  so  in  adolescents,  and  comparatively  slight  in 
those  who  have  reached  adult  age." 

In  that  paper  Dr  John  Thomson  directs  attention  to  the  fact, 
which  was  very  marked  in  Case  XXXVI.,  viz.,  that  the  spinal 
curvature  and  the  tendency  to  bowlegs  are  apt  to  be  increased 
during  the  thyroid  treatment.      He  says  : — 

"  This  tendency  to  bowlegs  may  be  due  to  too  large  doses  of  thyroid  or  to 
some  other  indiscretion  in  the  treatment.  It  certainly  seems  likely  to  constitute 
a  troublesome  complication  in  the  management  of  adolescent  cretins.  We 
should  try  to  avert  it  by  keeping  the  patient  from  walking  too  much  at  first  and 
by  giving  him  strengthening  diet  and  medicine.  Practically,  however,  these 
indications  may  be  extremely  difficult  to  fulfil.  On  the  one  hand,  the  great  in- 
crease of  energy  renders  it  almost  impossible  to  keep  the  patient  off  his  feet, 
and,  on  the  other  hand,  cretins  are  often  extremely  difficult  to  diet  or  to  dose 
owing  to  their  very  fastidious  tastes  and  the  lax  discipline  to  which  they  have 
always  been  accustomed." 

These  considerations  show  the  great  importance  of  early 
•diagnosis  and  of  early  treatment. 

The  Treatment  of  Myxcedema  and  Sporadic  Cretinism. 

In  the  article  on  Myxcedema,  in  my  Atlas  of  Clinical  Medi- 
cine, published  in  May  1891,  I  made  the  following  statements  : — 

"  The  statements  which  are  to  be  found  in  the  text-books,  and 
indeed  in  the  best  and  most  extended  monographs  on  the  treat- 
ment of  myxcedema,  are  of  the  most  meagre  and  unsatisfactory 
character.  .  .  .  For  the  reasons  given  above,  I  cannot  help 
hoping  that,  if  attacked  in  a  sufficiently  early  stage,  the  disease  may, 
perhaps,  in  the  future  be  found  to  be  more  amenable  to  treatment 
.than  we  at  present  believe." 


324  DISEASES   OF   THE   BLOOD   GLANDS. 

I  then  go  on  to  say  that  from  a  consideration  of  the  etiology, 
pathology,  and  clinical  history  of  myxcedema,  and  the  effects  of 
removal  of  the  thyroid  gland  both  in  man  and  the  lower  animals, 
it  would  appear  that  the  main  objects  of  treatment  should  be  : — 
(i)  To  arrest  the  degenerative  and  atrophic  process  in  the  gland  ; 
(2)  to  protect  the  patient  against  anything  which  is  likely  to  aggra- 
vate the  symptoms  or  facilitate  the  progress  of  the  disease  ;  (3)  to 
endeavour  (as  Victor  Horsley  has  suggested)  to  supplement  the 
function  of  the  atrophied  and  degenerated  gland  by  grafting  a  new 
and  healthy  thyroid  gland  tissue  into  the  body  of  the  patient. 

When  I  wrote  that  article  I  had  no  doubt  whatever  that  the 
myxcedematous  condition  was  due  to  defective  thyroid  secretion. 

In  summing  up  the  lengthened  argument  with  regard  to  the 
pathology  of  the  disease,  I  state  : — "  To  my  mind,  then,  it  is  satis- 
factorily and  conclusively  proved,  both  by  clinical  and  post-mortem 
evidence  in  cases  of  primary  myxcedema  (by  the  results  of  extir- 
pation of  the  goitrous  thyroid  gland  in  man  and  by  the  results  of 
extirpation  of  the  thyroid  gland  in  animals),  that  the  essential 
cause  of  myxcedema  is  abolition  of  the  function  of  the  thyroid 
gland." 

Shortly  after  this  article  appeared  (October  1891),  Dr  George 
Murray  introduced  the  subcutaneous  injection  plan  of  treatment, 
and  conclusively  proved  that  the  secretion  of  the  thyroid  gland, 
when  introduced  into  the  bodies  of  myxcedematous  patients,  in  this 
way,  produced  rapid  disappearance  of  all  the  myxcedematous  symp- 
toms and  cured  the  disease,  for  if  the  treatment  is  regularly  and 
steadily  continued  the  patient  is  maintained  in  a  condition  of  good 
health.     This — the  hypodermic  method — was  a  great  advance. 

In  October  1892,  Drs  Hector  Mackenzie  and  Fox  found  that  the 
same  therapeutic  effects  (disappearance  of  the  myxcedematous  symp- 
toms and  cure  of  the  disease)  are  produced  when  the  secretion  of  the 
thyroid  gland  is  introduced  into  the  stomach.  This  was  a  still  further 
advance,  for  the  subcutaneous  injection  method  is  not  only  irksome 
and  troublesome  to  the  patient,  but,  unless  extreme  care  is  taken, 
is  apt  to  be  followed  by  injurious  results  (local  inflammation, 
abscess,  septic  poisoning,  etc.). 

The  effects  produced  in  cases  of  myxcedema  by  the  introduc- 
tion into  the  organism  of  a  relatively  minute  quantity  of  thyroid 
extract,  the  rapidity  with  which  all  the  characteristic  symptoms  of 
the  disease  disappear  under  the  influence  of  the  thyroid  treatment, 
and  the  extraordinary  improvement,  both  in  the  physical  and  mental 
condition,  of  sporadic  cretins,  which  results  from  the  regular  and 
prolonged  administration  of  thyroid  extract,  are    very  remarkable. 


MYXCEDEMA.  325 

Indeed,  it  is  no  exaggeration  to  say,  that  the  cure  of  myxcedema 
by  thyroid  treatment  is  one  of  the  greatest  therapeutic  achievements 
of  this  or  any  other  age,  and  that  the  flood  of  light  which  has  been 
thrown  upon  the  functions  of  the  thyroid  gland  by  the  experimen- 
tal, pathological,  and  clinical  researches  of  the  past  few  years,  and 
by  the  marvellous  therapeutic  results  which  have  been  obtained  in 
cases  of  myxcedema  and  sporadic  cretinism  by  the  administration  of 
thyroid  extract,  has  opened  up  a  wide  field  of  investigation,  alike  for 
the  physiologist,  the  pathologist,  and  the  physician. 

That  the  myxedematous  symptoms  undergo  immediate  im- 
provement after  the  introduction  of  a  portion  of  living  thyroid 
gland  into  the  abdominal  cavity  or  into  the  subcutaneous  cellular 
tissue  (the  transplantation  plan  of  treatment),  and  that  myxcedema 
can  be  cured  by  the  subcutaneous  injection  of  a  liquid  extract  of  the 
thyroid  gland,  were  remarkable  discoveries  ;  but  that  the  adminis- 
tration of  the  thyroid  gland,  given  either  in  the  raw  or  partly 
cooked  state,  in  the  form  of  a  liquid  extract,  or  even  of  a  dry 
powder,  is  able,  when  introduced  into  the  body  through  the  stomach, 
to  cause  the  rapid  disappearance  of  all  the  myxedematous  symp- 
toms and  to  lead  to  the  cure  of  the  disease,  seems  to  me  still  more 
extraordinary. 

At  the  end  of  this  article  I  have  appended  the  notes  of  thirty- 
four  cases  of  myxcedema  and  of  five  cases  of  sporadic  cretinism, 
which  I  have  had  the  opportunity  of  treating  during  the  past  six 
years — i.e.,  since  the  plan  of  thyroid  feeding  was  introduced  (see 
also  Table  9).  The  remarkable  results  obtained  in  these  cases 
speak  more  eloquently  than  words  can  do  as  to  the  specific  value 
of  the  remedy.  The  husband  of  one  of  my  patients  wrote  me  : — 
"  That  thyroid  extract  appears  to  be  the  veritable  elixir  vitce  !  " 

The  full  details  of  most  of  these  were  published  in  the  Edin- 
bnrgJi  Hospital  Reports  for  the  year  1895,  P-  u6.  At  the  end  of 
that  paper  I  summarised  the  results  as  follows  : — 

Therapeutic  Conclusions. — The  points  which  seem  to  me  of 
most  importance  in  connection  with  the  thyroid  treatment  of 
myxcedema  and  sporadic  cretinism  are  as  follows  : — 

1.  Myxcedema  and  sporadic  cretinism  being  due  to  a  deficiency 
of  thyroid  secretion  (degeneration,  atrophy,  or  absence  of  the  thyroid 
gland),  the  thyroid  extract  is  to  be  regarded  as  a  true  specific  for 
the  cure  of  the  disease. 

2.  The  specific  effect  may  be  produced  either  by  (a)  transplant- 
ing the  living  gland  into  the  body  of  the  patient ;  {&)  the  sub- 
cutaneous injection  of  a  liquid  extract  of  the  gland  ;  or  (c)  the 
introduction  of  the  gland,  either  in  the  raw  or  partly  cooked  state, 


Table  9. — Showing  Results  of  Treatment  in  Thirty  Cases  of 
Myxgedema  and  Five  Cases  of  Sporadic  Cretinism. 


» 

^2 

Date  of 

.2 

tn    C 

1 

Dose  of  Thyroid 

th  of  Time 
has  Elapsed 
Treatment 
ommenced. 

M 

JJ 

Commence- 

O   V 

Immediate 

Subsequent 

Ultimate 

Extract  which 

Cause  of 

H 

c  c 

.2    M 

ment  of 

Result. 

Progress. 

Result. 

Patient  continues 

Death. 

r 

2." 

Treatment. 

5»S 

to  take. 

Mj3    UU 
B   0  u  »i 

0 
V. 

d 

2 

1 

< 

ft 

r 

1— J    ^   m   £ 

I 

52 

12  years 

Dec.  22,  1892 

? 

Rapid  disap.  of 

Died  4  weeks 

Death. 

Syncope* 

myx.  symptoms. 

after  treat- 
ment com. 

2 

3 

53 

20      ,, 

Jan.  25,  1893 

? 

Ditto. 

Cont'd  well. 

Rem'ns  well. 

5  grains  daily. 

6  years. 

3 

4 

26 

4          I! 

Jan.  14,  1893 

21  lbs. 

Ditto. 

Ditto. 

Ditto. 

■z\  grains  daily. 

°       ,, 

4 

5 

tl 

4       .. 

Feb.  9,  1893 

? 

Ditto. 

Ditto. 

Ditto. 

5  grains  every  3rd 
or  4th  day. 

6       „ 

5 

6 

40 

2      ,, 

? 

9 

Ditto. 

Relapse  :    re- 
mains well. 

Ditto. 

10  grs.  ext.  daily. 

6      „ 

6 

9 

48 

5      .. 

Nov.  8,  1892 

18  lbs. 

Ditto. 

Cont'd  well.f 

Deaths^yrs. 
after  treat- 
ment com. 

Cerebral 
hsemorr. 

7 

10 

33 

3       >> 

Jan.  5,  1893 

7%  lbs. 

Ditto. 

Ditto. 

Rem'ns  well. 

10  grains  daily. 

6      „ 

8 

11 

5i 

3       n 

Jan.  18,  1893 

? 

Improvement. 

Developed 
phthisis. 

Death. 

Phthisis. 

9 

12 

5i 

3      ,, 

Jan.  23,  1893 

? 

Rapid  disap.  of 
myx.  symptoms. 

Cont'd  well. 

Rem'ns  well. 

5  grains  every  3rd 
day. 

6      „ 

10 

13 

5° 

3      .. 

Jan.  27,  1893 

? 

Ditto. 

Ditto. 

Ditto. 

5  grs.  every  other 
day. 

6      ,. 

11 

M 

73 

34      ,. 

June  5,   1893 

? 

Some  improve- 

In statu  quo. 

Died  6  inths. 

Syncope  % 

ment. 

after  treat- 
ment com. 

12 

15 

51 

20      ,, 

June  30, 1893 

19  lbs. 

Rapid  disap.  of 
myx.  symptoms. 

Cont'd  well. 

Rem'ns  well. 

10  grains  twice  or 
thrice  a  week. 

5*     .1 

13 

l6 

So 

2       ,, 

July  26,  1893 

? 

Ditto. 

Ditto. 

Ditto. 

J  raw  gland  twice 
a  week. 

5*     ,, 

M 

r7 

55 

2       „ 

Aug.  6,  1893 

? 

Ditto. 

Ditto. 

Ditto. 

5  grs.  every  other 
day. 

5i    ,. 

IS 

18 

67 

4      ii 

Oct.  12,  1893 

? 

Ditto. 

Ditto. 

Ditto. 

5  grains  daily. 

5i     .. 

16 

19 

40 

4       .. 

Jan.  10,  1894 

? 

Ditto. 

Cont'd     well, 
but  d'v'lop'd 
melancholia 

Ditto. 

5  grs.  every  other 
day. 

S      ., 

17 

20 

60 

2       „ 

April  s,  1894 

? 

Ditto. 

Cont'd  well. 

Ditto. 

i\  grains  daily. 

4S     ,1 

18 

21 

3i 

3      .. 

May  9,  1894 

? 

Ditto. 

Ditto. 

Ditto. 

5  grs.  every  other 
day. 

4*     .. 

19 

22 

60 

3      ,. 

July  8,   1894 

? 

Ditto. 

Ditto. 

Ditto. 

5  grains  daily. 

43     n 

20 

23 

66 

7      >. 

Aug.  9,  1894 

? 

Ditto. 

Ditto. 

Ditto. 

5  grs.  every  other 
day. 

4i    .. 

21 

24 

36 

6      „ 

Nov.  15.1894 

17  lbs. 

Ditto. 

Ditto. 

Ditto. 

5  grains  daily. 

4       ii 

22 

25 

33 

3      .. 

Dec.  13,  1894 

28  lbs. 

Ditto. 

Relapse. 

Ditto. 

10  grains  daily. 

4       11 

23 

26 

1 2 

3      » 

Mar.  3,  1895 

J 

Ditto. 

Cont'd  well. 

Ditto. 

5  grains  daily. 

35     ,. 

-4 

27 

5° 

12      ,, 

May  15, 1895 

? 

Gradual  improve- 
ment. 

Ditto. 

Ditto. 

10  grains  daily. 

3iJ     11 

-5 

-".' 

64 

3       11 

Mar.  29, 1S96 

20  lbs. 

Rapid  disap.  of 
myx.  symptoms. 

Ditto. 

Ditto. 

5  grains  daily. 

2!     1, 

26 

3r< 

32 

4      >> 

Feb.  12,  1897 

16  lbs. 

Ditto. 

Ditto. 

Ditto. 

5  grains  once  or 
twice  a  week. 

l|     ,, 

27 

31 

41 

14      11 

Feb.  1893 

? 

Ditto. 

Cont'd    fairly 
well. 

Death. 

Ulcer'nof 
stom.,etc. 

28 

3« 

|2 

2       ,, 

Apr.  15,  1897 

15  J  lbs. 

Ditto. 

Cont'd  well. 

Rem'ns  well. 

9 

ii    „ 

29 

33 

43 

4imnths 

May  31,  1897 

14!  lbs. 

Slow  but  gradual 
improvement. 

Cont'd    fairly 
well. 

R'm'ns  fairly 
well:  suffers 
from  heart, 
etc. 

0 

1^    ,, 

30 

34 

14 

4  years 

Fell.  12,  1897 

? 

Rapid  disap.  of 
myx.  symptoms. 

Cont'd  well. 

Rem'ns  well. 

5  grains  daily. 

if    ,, 

3' 

35 

8J 

81    „ 

Jan.  10,  1893 

Ditto. 

Ditto. 

Still  improv. 

5  grains  daily. 

6      ,, 

32 

/ 

16J 

16J?  „ 

Apr.   i,  1893 

3J  lbs. 

Ditto. 

Slight  improve- 
ment. 

In  statu  quo. 

Nil. 

5*     ., 

33 

37 

3 

4.1     „ 

Mar.  30, 1893 

Ditto. 

Cont'd  well. 

Still  improv. 

3  grains  daily. 

5i     .. 

34 

V 

4 

3-i    ,, 

July  2,   1894 

•> 

Ditto. 

Ditto. 

Ditto. 

5  grs.  every  other 

day. 
5  grs.  every  other 

3i    .- 

35 

39 

2* 

2j      „ 

Aug.  17,  1894 

? 

Slow  disap.  of 

Ditto. 

Ditto. 

3*     .. 

myx.  symptoms. 

day. 

*  Total  dose  of  thyroid  administered  =  2!  sheeps'  thyroids  in  the  course  of  three 
fortnight  before  patient's  death.  On  post-mortem  examination,  thyroid  gland 
coronary  arteries  atheromatous  ;  heart  muscle  extremely  degenerated. 

t  Refused  to  take  thyroid  for  two  months  before  death.     J  So  long  as  continued  to  take  the  thyroid  extract  regularly. 


weeks.     Thyroid  treatment  stopped  a 
enlarged,    pituitary   gland   enlarged  ; 


MYXGEDEMA.  327 

in  the  form  of  a  liquid  extract  or  of  a  dry  powder,  into  the  body 
through  the  stomach. 

3.  The  effects  of  transplantation — the  first  step  in  the  develop- 
ment of  the  thyroid  treatment — are  merely  temporary,  owing  to  the 
fact  that  the  transplanted  portion  of  gland  usually  dies  in  the  course 
of  a  short  time  and  is  absorbed.  If  the  transplanted  portion  of  gland 
could  be  engrafted  so  that  it  permanently  lived  and  continued  to 
secrete,  the  transplantation  plan  of  treatment  would,  no  doubt,  be  the 
best,  since  the  result  would  be  permanent  and  no  further  treatment 
would  be  required.  But  even  if  survival  of  the  engrafted  piece  of 
thyroid  gland  could  be  ensured,  there  would  still  be  the  chance,  as 
Murray  has  pointed  out,  of  it  becoming  in  its  turn  diseased,  i.e., 
affected  with  the  same  cirrhotic  changes  which  produced  the  original 
degeneration  and  atrophy  of  the  gland  belonging  to  the  patient. 
Fortunately  transplantation  is  entirely  unnecessary,  for  thyroid 
feeding  is  easy,  cheap,  and  perfectly  satisfactory  in  its  results. 

The  subcutaneous  injection  method,  which  was  the  next  step  in 
the  development  of  the  treatment,  has  no  advantages  over  thyroid 
feeding,  and  has  several  grave  disadvantages,  viz.,  the  injection  is 
attended  with  some  pain  ;  it  requires  to  be  carefully  performed,  and 
should  only  be  practised  by  a  skilled  observer  ;  it  not  unfrequently 
gives  rise  to  local  irritation  and  inflammation,  and  it  may  be,  and 
has  actually  been,  followed  by  general  sepsis  and  death. 

Thyroid  feeding,  which  is  quite  as  efficacious,  is  consequently 
the  method  of  administration  which  should  be  preferred. 

4.  The  dry  extract  in  the  form  of  tabloids,  is  an  active  and 
thoroughly  reliable  preparation  ;  its  activity  does  not  appear  to  be 
impaired  by  keeping ;  the  dose  can  be  accurately  regulated  ;  it  is 
consequently  a  most  convenient  preparation,  and  is  the  one  which 
I  now  almost  invariably  employ.  Personally,  I  have  had  little 
experience  with  thyrocol  which  Dr  Robert  Hutchison  claims  is  the 
active  principle  of  the  thyroid  secretion  ;  but  in  the  two  cases  (one 
case  of  myxcedema  in  an  adult  and  one  case  of  sporadic  cretinism) 
in  which  I  have  tried  it,  while  it  produced  marked  headache,  it  cer- 
tainly appeared  to  me  to  be  less  efficacious  than  the  ordinary  tabloids 
of  dried  extract. 

5.  Most  patients  affected  with  myxcedema  and  sporadic  cretinism 
are  very  susceptible  to  the  action  of  the  thyroid  extract ;  and  since 
it  is  rarely,  if  ever,  advisable  in  the  treatment  of  these  diseases  to 
produce  the  full  physiological  effects  of  the  remedy  (acute  thy- 
roidism),  a  small  dose  should  be  first  administered.  If  the  pre- 
liminary (small)  dose  is  insufficient  to  produce  any  reaction  or 
improvement,  the  dose  should  be  gradually  but  carefully  increased. 


328  DISEASES   OF   THE   BLOOD   GLANDS. 

In  cases  of  adult  myxcedema,  I  usually  commence  by  giving  5 
grains  of  the  dry  powder  once  daily.  In  cases  of  sporadic  cretinism, 
I  usually  commence  by  giving  f  to  ii  grain  once  daily,  in  accord- 
ance with  the  age  of  the  child.* 

In  some  of  my  earlier  cases  the  dose  which  was  administered 
was  too  large,  the  result  being  acute  thyroid  ism  and  serious  dis- 
turbance (see  Cases  IX.,  X.,  and  XXXVII.).  The  debility  and  cardiac 
depression  which  attend  this  acute  thyroidism  are  often  very  great, 
and  may,  in  old  patients  and  in  patients  suffering  from  diseased 
hearts  or  arteries,  be  attended  with  danger. 

Most  patients  suffering  from  myxcedema  and  sporadic  cretinism 
seem  to  be  much  more  susceptible  to  the  action  of  thyroid  extract 
than  healthy  people  and  patients  suffering  from  skin  diseases 
(psoriasis,  ichthyosis,  etc.). 

In  most  cases  of  myxcedema,  unpleasant  symptoms  and  acute 
thyroidism  are  apt,  in  my  experience,  to  be  produced  if  the  dose 
exceeds  4  tabloids  daily  Q  of  a  sheep's  thyroid  gland) ;  but  in 
several  cases  of  psoriasis  and  ichthyosis  I  have  given  20,  30,  40,  and 
in  one  case  even  74  tabloids  (a  dose  equal  to  one,  two,  or  even  five 
average  sheep's  thyroid  glands)  per  diem. 

6.  In  cases  of  adult  myxcedema  the  objects  of  treatment 
are : — 

(a)  To  remove  the  myxcedematous  condition  without  producing 
undue  or  serious  depression  of  the  action  of  the  heart  and  strength, 
and  without  producing  acute  thyroidism. 

In  most  cases  of  myxcedema  1  (5-grain)  tabloid,  three  times 
daily  (  =  T36-  of  an  average  sheep's  thyroid  gland)  is  the  maximum 
dose  which  is  required  during  this,  the  first,  stage  of  the  treatment. 

I  have  only  found  it  necessary  to  give  large  doses  of  the  remedy 
in  a  few  cases  of  myxcedema.  In  Case  XXV.,  for  example,  13 
tabloids  (  =  f  of  a  whole  gland)  were  given  for  several  days  in 
succession  without  producing  any  distinct  symptoms  of  thyroidism 
except  vomiting. 

(b)  After  the  myxcedematous  symptoms  are  removed,  to  keep  the 
patient  in  good  health  and  prevent  tlie  redevelopment  of  the  disease. 

In  most  cases  of  adult  myxcedema,  1  (5-grain)  tabloid  every  day 
or  every  second  or  third  day  is  sufficient  for  this  purpose  ;  but  the 
dose  which  is  required  in  each  individual  case  can  only  be  deter- 
mined by  experiment  and  observation. 


*  Burroughs,  Wellcome  &  Co.  supply  two  tabloids — one,  suitable  for  adults, 
contains  5  grains  of  the  dry  extract  =  TVth  of  an  average  sheep's  thyroid  ;  the 
other,  suitable  for  children,  contains  \\  grains  of  the  dry  extract. 


MYXCEDEMA.  329 

So  far  as  our  present  knowledge  enables  us  to  judge,  the 
systematic  administration  of  the  remedy  must  be  continued  through- 
out the  whole  future  life  of  the  patient ;  but  this  is  no  hardship  ; 
the  remedy  is  cheap,  and  is  as  easily  taken  after  or  at  a  meal  as  a 
dinner  pill  or  a  pinch  of  salt. 

So  far  as  we  know,  a  thyroid  gland  which  is  once  atrophied  and 
destroyed  by  the  pathological  process  which  is  present  in  myxce- 
dema,  is  never  restored,  but  it  is  not  unlikely  that  future  observation 
may  show  that  in  some  of  the  cases  in  which  all  the  typical  symp- 
toms of  myxoedema  are  present,  the  gland  function  is  restored,  at 
all  events  in  some  degree  ;  in  other  words,  it  is  not  improbable  that 
the  function  of  the  thyroid  gland  may  be  temporarily  arrested, 
suspended,  or  interfered  with,  and  that  myxedematous  symptoms 
may  be  the  result  of  functional  or  structural  changes  of  a  tem- 
porary and  removable  kind.  I  do  not  see  that  it  is  necessary  to 
suppose  that  in  every  case  in  which  myxedematous  symptoms  are 
developed,  the  secreting  tissue  of  the  gland  is  permanently  and  hope- 
lessly destroyed. 

7.  In  cases  of  sporadic  cretinism,  the  objects  of  treatment 
are: — 

(a)  To  remove  the  myxcedematous  condition  without  producing 
undue  depression  of  the  action  of  the  heart  and  strength,  and  without 
producing  acute  thyroidism. 

In  most  cases  of  sporadic  cretinism,  1  (5-grain)  tabloid,  once 
daily  (  =  TV  of  an  average  sheep's  thyroid  gland),  is  a  sufficient  dose 
during  this  stage  of  the  treatment. 

(b)  To  promote  the  development  of  the  body  and  mind. 

{c)  To  prevent  the  redevelopment  of  the  myxoedematous  symptoms  ; 
and  to  keep  the  patient  in  good  health  until  the  full  development  of 
body  and  mind  is  attained,  and  dialing  the  remainder  of  life. 

One  (5-grain)  tabloid  every  second,  third,  or  fourth  day  is  pro- 
bably a  sufficient  dose  during  this,  the  second,  stage  of  the  treatment. 
But  it  is  impossible  to  speak  with  absolute  certainty  on  this  point. 
The  length  of  time  which  has  as  yet  elapsed  since  the  introduction 
of  the  thyroid  treatment  is  insufficient  to  allow  of  a  definite 
statement. 

And  I  may  here  say  that  as  yet  we  do  not  know  what  effect  the 
treatment  may  ultimately  produce  in  respect  to  the  bodily  and 
mental  development  in  cases  of  sporadic  cretinism. 

Much,  no  doubt,  will  depend  upon  the  age  of  the  patient  when 
the  treatment  is  commenced,  and  upon  the  severity  of  the  case. 

In  slight  cases,  in  which  the  treatment  is  commenced  at  an  early 
stage  of  the  disease,  there  is  every  reason  to  hope,  judging  from 


3$0  DISEASES   OF   THE   BLOOD    GLANDS. 

the  remarkable  effects  which  can  be  produced  in  two  or  three  years, 
that  a  very  considerable  development — possibly  the  full  develop- 
ment— both  of  the  body  and  mind,  will  be  ultimately  attained. 

But  in  very  severe  cases,  in  which  the  disease  is  of  long  duration, 
as  in  Case  XXXVI.,  the  degree  of  improvement  which  can  be  pro- 
duced will  probably  be  small.  These  considerations  show  the 
great  importance  of  early  diagnosis. 

8.  In  most  cases  both  of  mxycedema  and  sporadic  cretinism,  and 
in  most  cases  of  skin  disease  (psoriasis,  ichthyosis,  etc.),  the  sus- 
ceptibility to  the  action  of  the  drug  seems,  so  far  as  my  present 
experience  enables  me  to  judge,  to  diminish  somewhat,  rather  than 
to  increase,  after  the  remedy  has  been  given  for  a  considerable 
length  of  time. 

I  have,  however,  met  with  several  exceptions  to  this  statement. 
The  most  remarkable  is  Case  XI.  From  the  commencement  of 
the  treatment  this  patient  was  very  susceptible  to  the  action  of  the 
remedy.  After  the  drug  had  been  administered  for  some  months, 
the  susceptibility  became  so  great  that  ^  of  a  tabloid  ( =  r^s  of  a 
gland)  produced  distinct  effects  (flushing  of  the  face,  a  feeling  of 
uneasiness  and  tension  in  the  head,  a  rise  of  the  temperature  and 
pulse),  even  when  the  remedy  was  given  without  the  patient's  know- 
ledge. The  effect  of  these  minute  doses  was  so  marked,  that  the 
medical  attendant  volunteered  the  statement  that  he  believed  one 
whole  tabloid  Avould  have  killed  the  patient  at  this  stage  of  the 
case. 

Between  these  two  extremes — £  of  a  tabloid  (in  this  exceptional 
case  of  myxcedema)  and  74  tabloids  (the  largest  dose  which  I  have 
given  in  a  case  of  psoriasis) — the  therapeutic  range  is  enormous. 
Hence  the  necessity  of  caution  in  prescribing  the  remedy,  and  of 
giving  small  doses  at  the  commencement  of  the  treatment. 

9.  In  most  cases  of  myxoedema  and  sporadic  cretinism  the 
beneficial  effects  of  the  remedy  are  rapidly  manifested. 

In  some  cases  a  distinct  change  for  the  better  is  apparent  after 
the  administration  of  a  few  grains  of  the  dried  extract.  In  one 
case  of  sporadic  cretinism,  for  example  (Case  XXXVIII.),  the 
myxcedematous  swelling  of  the  eyelids  and  lips  was  distinctly  less, 
the  expression  was  much  brighter,  and  the  colour  of  the  lips  and 
face  distinctly  improved,  after  the  administration  of  two  very  small 
doses  (=  1  \  grains  in  all)  of  the  dried  extract. 

Now,  if  a  visible  external  change,  a  relatively  coarse  result,  can 
be  produced  by  \l  grains  of  the  dried  extract,  it  must,  I  think,  be 
admitted  that  a  distinct  physiological  effect  can  be  produced  by, 
relatively  speaking,  very  minute  doses. 


MYXCEDEMA.  331 

Nor  is  the  immediate  effect  altogether  confined  to  cases  of  myxce- 
dema  and  sporadic  cretinism,  for  in  one  of  my  cases  of  psoriasis  a 
distinct  improvement  was  observed  in  the  condition  of  the  skin 
after  the  administration  of  two  small  doses  of  the  extract  (10  drops 
of  Brady  &  Martin's  liquid  extract  in  all). 

Further,  in  cases  of  myxcedema,  a  distinct  improvement  has 
been  noted  in  the  course  of  a  few  hours  after  the  transplantation 
plan  of  treatment. 

10.  In  cases  of  myxcedema,  it  is  advisable  to  keep  the  patient 
in  bed  during  the  first  three  or  four  weeks  of  the  treatment.  Old 
and  debilitated  persons  should  remain  in  bed  for  a  much  longer 
period  of  time,  and  should  be  carefully  warned  against  getting  up 
suddenly,  lest  fainting  or  cardiac  syncope  should  occur. 

11.  In  all  cases  of  myxcedema  in  which  the  action  of  the  heart 
becomes  much  enfeebled  during  the  thyroid  treatment,  it  is  advis- 
able, I  think,  to  give  cardiac  tonics  and  stimulants  (strychnine, 
digitalis,  strophanthus,  alcohol,  etc.). 

12.  During  the  first  stage  of  the  treatment  of  cases  of  myxcedema 
and  sporadic  cretinism,  I  usually  keep  the  patient  on  a  milk  diet,  or 
a  milk-fish-white-meat  diet. 

13.  Immediate  effects  of  the  treatment. — The  more  marked 
effects  of  the  treatment  in  cases  of  myxcedema  and  sporadic  cretinism 
are  : — Rapid  disappearance  of  the  myxcedematous  swelling  ;  loss 
of  weight ;  increased  liveliness  and  activity  ;  a  rise  in  temperature 
and  pulse  ;  a  feeling  of  increased  wellbeing  ;  disappearance  of  the 
feeling  of  cold ;  restoration  of  the  secretion  of  sweat ;  increased 
appetite  ;  disappearance  of  the  constipation  ;  improvement  in  the 
general  nutrition,  and  especially  in  the  nutrition  of  the  skin  and  its 
appendages  ;  and,  in  sporadic  cretins,  a  rapid  growth  of  the  body, 
and  a  rapid  development  of  the  mental  faculties. 

The  first  effects  of  small  doses  are  usually : — Decrease  of  the 
swelling  of  the  eyelids,  lips,  and  tongue  ;  increased  brightness  of 
expression  and  liveliness  ;  and  improved  colour  in  the  lips  and 
face.  These  alterations  are  usually  quickly  followed  by  a  rise  in 
temperature  and  pulse  ;  but  the  rise  in  temperature  in  some  cases 
does  not  take  place  until  later,  or  is  only  very  slight.  With  the 
continuance  of  the  treatment  the  myxcedematous  swelling  subsides, 
and  finally  disappears  ;  the  skin  becomes  smooth  ;  the  secretion  of 
sweat  is  re-established  ;  and  a  feeling  of  pleasant  warmth  replaces 
the  sensation  of  cold  which  the  patient  previously  experienced. 
The  disappearance  of  the  increased  sensibility  to  cold  which  is  such 
a  striking  symptom  of  the  disease  is  one  of  the  most  remarkable 
results  of  the  treatment.     One  of  my  patients,  a  medical  man,  who 


332  DISEASES   OF   THE   BLOOD   GLANDS. 

before  the  treatment  was  commenced  "  felt  the  cold  intensely,"  and 
whose  "  hands  and  feet  were  always  icy  cold,"  wrote  me  a  month 
after  the  commencement  of  the  treatment  saying,  "  I  have  lost  the 
cold  feeling — in  fact  I  always  feel  warm  now."  This  patient  re- 
sumed his  professional  duties  three  and  a  half  months  after  the 
treatment  was  commenced  ;  three  weeks  later  he  wrote  me,  on 
22nd  March,  1894,  "  I  stood  the  intense  cold  which  we  have  re- 
cently had  as  well  as  my  neighbours  I  think,  and  where  I  was 
staying  we  had  for  some  time  a  register  130  below  zero  (45  degrees 
of  frost)." 

The  loss  of  weight  which  occurs  during  the  course  of  the  treat- 
ment is  in  many  cases  of  myxcedema  very  great.  Thus,  in  Case 
IV.,  the  patient  lost  21  lbs.;  in  Case  IX.,  18  lbs. ;  in  Case  XV.,  19 
lbs.  ;  in  Case  XXIV.,  17  lbs.  ;  and  in  Case  XXV.,  20  lbs. 

The  administration  of  one  or  two  large  doses  of  thyroid  extract 
is,  in  some  cases  of  myxcedema  and  sporadic  cretinism,  attended 
with  most  marked  diminution  of  the  myxcedematous  swelling  and 
abdominal  distension.  Thus,  in  Case  XXXVII.  (sporadic  cre- 
tinism), after  three  (10-drop)  doses  of  Brady  &  Martin's  liquid 
extract,  the  abdomen,  which  had  previously  measured  19  inches, 
only  measured  14!  inches. 

This  rapid  loss  of  weight  is  usually  attended  with  a  feeling  of 
great  debility,  languor,  and  depression  ;  the  heart's  action  and  the 
pulse  may  become  very  feeble ;  and  it  is  not  uncommon  for  the 
patients  to  faint  after  getting  out  of  bed  suddenly,  rising  from  the 
recumbent  to  the  erect  position,  or  after  a  free  movement  of  the 
bowels. 

Death  may  actually  result  from  sudden  failure  of  the  Jieart's 
action  in  such  conditions  (see  Case  I.).  In  old  and  debilitated 
persons,  and  in  patients  whose  hearts  are  diseased  or  weak,  it  is 
therefore  of  the  utmost  importance  to  guard  against  the  occurrence 
of  fainting  during  the  course  of  the  treatment,  and  to  sustain  the 
action  of  the  heart  by  the  administration  of  cardiac  tonics  and 
stimulants. 

Further,  it  should  be  remembered  that  anosmia  is  apt  to  be 
produced  by  large  doses  of  the  remedy.  In  Case  IX.,  for  example, 
the  red  blood-corpuscles  and  the  haemoglobin  underwent  a  marked 
diminution  during  the  period  of  acute  thyroidism,  but  rapidly 
increased  under  the  subsequent  administration  of  small  doses  of 
the  remedy.     The  successive  estimations  were  as  follows  : — 


MYXOEDEMA. 


Red 
Corpuscles. 

Hsemoglobin. 

October  28  (before  treatment)  - 
November  28  (after  acute  thyroidism) 
December  21  (during  subsequent  improvement) 
January  13  (on  discharge)          _         .         . 

3,820,000 
2,620,000 
3,850,000 
4,310,000 

65  per  cent. 

54       „ 

68       „ 
7o 

After  the  myxcedematous  swelling  has  disappeared,  and  the 
patient  begins  to  go  about  again,  it  frequently  happens  that  the 
feet  swell.  This  oedema,  which  is  merely  the  result  of  the  anaemia 
and  cardiac  enfeeblement,  may  be  thought  to  indicate  a  return  of 
the  myxcedematous  condition.  Dr  X.,  for  example  (Case  XXIV.), 
became  alarmed  when  he  noticed  the  occurrence  of  this  oedema  of 
the  feet.  The  oedema  of  the  feet  usually  passes  off  in  the  course 
of  a  few  weeks,  when  the  patient  regains  strength ;  it  should 
be  treated  by  rest,  and  the  administration  of  cardiac  tonics  and 
stimulants. 

When  the  myxcedematous  condition  is  completely  cleared  away, 
the  alteration  in  the  appearance  of  the  patients  is  in  many  cases  so 
great  that  their  friends  and  relatives  fail  to  recognise  them.  In 
several  of  my  own  cases  I  had  absolutely  no  idea  who  the  patients 
were,  when  they  came  to  see  me  after  having  been  for  some  weeks 
or  months  under  treatment.  In  the  first  case  which  I  treated,  the 
patient's  daughter,  who  had  not  seen  her  since  the  treatment  was 
commenced,  said  to  the  nurse  :  "I  did  not  recognise  her  face  ;  I  saw 
that  her  body  was  the  same,  but  her  face  was  so  much  changed  that  I 
did  not  know  her." 

As  the  result  of  the  disappearance  of  the  myxcedematous 
condition  the  difficulty  in  swallowing  disappears. 

The  improvement  in  the  condition  of  the  general  nutri- 
tion, and  especially  in  the  nutrition  of  the  skin  and  its  appendages, 
is  one  of  the  most  striking  effects  of  the  treatment.  It  is 
no  exaggeration  to  say  that  myxcedematous  patients,  in  the 
course  of  a  few  weeks,  get  a  new  skin.  The  harsh,  rough, 
dry  skin  becomes  smooth,  soft,  and  moist ;  the  secretion  of  sweat 
is  re-established  ;  the  fine,  downy  hairs,  which  in  some  cases  of 
sporadic  cretinism  cover  the  forehead  and  back,  disappear ;  the 
warts  which  may  have  been  developed  on  the  surface  of  the  skin  in 
some  cases,  may  also  disappear.  The  dirty  encrusted  scalp  becomes 
clean  ;  the  hair  begins  to  grow  ;  and  the  scalp,  which  was  previously 


334  DISEASES   OF   THE   BLOOD    GLANDS. 

quite  bald,  may,  in  the  course  of  a  few  months,  become  covered 
with  a  luxuriant  crop  of  hair.  Case  III.  is  a  remarkable  illustration 
of  the  beneficial  effects  of  the  thyroid  treatment.  The  patient  was 
66  years  of  age  when  the  treatment  was  commenced,  and  she  looked 
older  than  her  years  ;  the  disease  was  of  twenty-four  years'  duration; 
her  arteries  were  atheromatous  ;  she  was  extremely  debilitated  ; 
the  scalp  was  almost  completely  bald  ;  in  short,  the  case  was  a  very 
aggravated  example  of  the  disease.  Two  and  a  half  years  after  the 
treatment  was  commenced  she  looked  at  least  ten  years  younger 
than  her  actual  age.  The  myxcedematous  symptoms  had  entirely 
disappeared.  She  had  regained  her  mental  activity ;  her  articula- 
tion was  sharp ;  she  was  able  to  attend  to  all  her  household  duties; 
her  head  was  covered  with  a  growth  of  long  black  hair,  which  was 
no  doubt  one  of  the  reasons  why  she  looked  so  much  younger  than 
her  actual  age.  Further,  after  recovering  from  the  myxcedema  she 
had  a  severe  attack  of  influenza,  complicated  with  pneumonia  ; 
during  this  illness  she  was  unconscious  for  two  or  three  days. 

In  two  of  my  cases  the  hair,  which  had  become  dark  and  black 
as  the  result  of  the  myxcedematous  condition,  regained  its  normal 
light  brown  colour  as  the  result  of  the  thyroid  treatment. 

Desquamation  is,  in  my  experience,  always  produced  in  those 
cases  of  myxcedema  and  sporadic  cretinism  in  which  large  doses  of 
the  extract  have  been  administered.  It  is  usually  best  marked  on 
those  parts  of  the  body  on  which  the  skin  is  thick — the  soles  of  the 
feet,  for  example. 

The  remarkable  improvement  in  the  condition  of  the  nutrition 
of  the  skin  and  the  desquamation  were  the  facts  which  led  me  to 
suggest  the  administration  of  thyroid  extract  in  psoriasis  and  other 
skin  diseases. 

The  improved  state  of  general  nutrition  is  remarkably  seen  in 
some  cases  of  sporadic  cretinism. 

The  rapidity  with  which  the  body  grows  during  the  earlier 
months  of  the  treatment,  is  in  many  cases  very  extraordinary. 
Thus,  in  Case  XXXV.  the  patient  grew  4  inches  in  one  year,  and  8 
inches  in  two  years  and  four  months  ;  in  Case  XXXVI  I.,  11  inches 
in  two  years  and  one  month  ;  in  Case  XXXVIII.,  4^  inches  in  n\ 
months  (in  this  case  the  remedy  was  very  irregularly  given  during 
several  months) ;  and  in  Case  XXXIX.,  61  inches  in  nine  months. 
In  some  of  my  cases  of  sporadic  cretinism  the  increased  growth 
of  the  hands  and  feet  was  proportionately  greater  than  the  increased 
growth  of  the  limbs  and  trunk. 

The  improvement  of  nutrition  is  also  manifested  by  the  rapid 
closure  of  the  anterior  fontanelle  and  by  the  cutting  of  the  teeth.     In 


MYXCEDEMA.  335 

Case  XXXVII.,  for  example,  the  patient,  who  before  the  treatment 
had  no  teeth,  at  the  end  of  eight  months  had  sixteen  teeth.  Further, 
in  cases  of  sporadic  cretinism,  the  teeth  which  are  cut  after  the  treat- 
ment is  commenced  are  (usually)  strong  and  healthy  ;  whereas  the 
teeth  which  are  cut  before  the  commencement  of  the  treatment,  in 
most  cases  decay  as  soon  as  they  come  through  the  gum. 

The  increased  appetite  which  occurs  as  the  result  of  the  treat- 
ment is,  in  some  cases  of  sporadic  cretinism,  very  noticeable.  Thus, 
in  Case  XXXV.,  in  the  course  of  three  weeks  the  patient  was  eating 
three  times  as  much  as  she  had  eaten  before  the  commencement 
of  the  treatment.  During  the  course  of  the  treatment  some  patients 
affected  with  sporadic  cretinism  get  very  fat. 

I  have  already  referred  to  the  disappearance  of  constipation, 
which,  in  most  cases  of  sporadic  cretinism,  is  very  marked.  In  Case 
XXXVII.,  for  example,  the  bowels,  which  had  never  been  opened 
without  the  aid  of  medicine  or  an  enema,  from  the  birth  of  the 
patient  until  the  treatment  was  commenced,  began  to  act  regularly 
and  naturally  in  the  course  of  a  few  weeks  after  the  regular  admini- 
stration of  the  thyroid  extract. 

In  some  cases  of  myxcedema,  the  menstruation,  which  had  pre- 
viously been  in  abeyance  for  many  months,  is  restored,  as  the  result 
of  the  treatment  ;  and  in  one  case,  as  I  have  already  pointed  out, 
the  breasts  filled  with  rich  milk  during  the  course  of  the  treatment. 

With  the  disappearance  of  the  myxedematous  symptoms  the 
articulation  becomes  sharp  and  quick;  the  voice  regains  its  normal 
tone,  and  patients  who  had  been  unable  to  sing  for  years  may  again 
get  their  voice.  The  mental  condition  is  at  the  same  time  enor- 
mously improved.  The  sleepy  feeling,  which  is  in  many  cases  a 
very  conspicuous  symptom,  disappears  ;  the  memory  is  regained, 
and  the  mental  powers  are  quickened  ;  in  some  of  the  asylum  cases, 
the  mental  deterioration,  which  was  so  marked  as  to  necessitate  their 
confinement,  disappears.  In  many  cases  of  sporadic  cretinism,  the 
rapid  development  of  the  mental  faculties  is  one  of  the  most  remark- 
able results  of  the  treatment. 

The  remarkable  improvement  in  the  memory  and  mental 
condition  is  well  illustrated  by  Case  XXVI.  This  patient  stated 
that  before  the  treatment  was  commenced  her  memory  and 
mental  powers  were  so  much  impaired  that  in  the  course  of  four 
weeks  she  was  unable  to  get  through  the  first  volume  of  a  three- 
volume  novel ;  she  could  not  remember  what  she  had  read  or  where 
she  had  left  off;  several  times,  in  going  from  her  lodgings  to  the 
baths  (at  Buxton),  which  were  close  at  hand,  she  lost  her  way. 
Two  and  a  half  months  after  the  commencement  of  the  treatment 


336  DISEASES   OF   THE   BLOOD    GLANDS. 

her  memory  and  mental  power  had  become  as  active  and  alert 
as  they  ever  had  been  ;  in  the  course  of  a  month  or  six  weeks 
she  read  a  number  of  books  of  different  kinds  and  remembered 
what  she  read. 

After  the  myxcedematous  symptoms  have  been  completely 
cleared  away,  the  increased  activity  and  capability  for  muscular  ex- 
ertion which  some  of  the  patients  manifest  is  very  remarkable.  In 
one  case  the  patient  was  able,  six  months  after  the  thyroid  treat- 
ment was  commenced,  to  ascend  a  hill  1,700  feet  high,  and  was  less 
distressed  than  her  husband  and  friends  who  accompanied  her. 
Another  patient,  three  months  after  the  treatment  was  commenced, 
stated  that  she  felt  like  a  new  person  ;  this  patient  was  able  at  the 
end  of  six  months  to  dismiss  her  housekeeper  and  companion  whom 
she  had  had  for  seven  years,  and  to  attend  to  all  her  household 
duties  herself. 

Alterations  in  the  urine. — The  albuminuria,  which  is  by  no 
means  uncommon  in  cases  of  myxcedema,  and  which  is  usually,  in 
my  experience,  functional,  generally  disappears  during  the  course 
of  the  treatment  (see  Cases  III.  and  XXIV.,  for  example). 

Several  observers  have  noted  an  increased  flow  of  urine  as  the 
result  of  the  administration  of  the  remedy,  but  in  none  of  the  cases 
which  I  have  carefully  observed  in  hospital  has  this  been  marked  ; 
and  in  some  cases  there  has  been  absolutely  no  increased  flow  of 
urine.     This  was  so  in  Case  XXV.,  for  example. 

In  one  case  the  rapid  disappearance  of  the  myxcedematous 
swelling  was  attended  with  an  enormous  excretion  of  mucus  and 
uric  acid  in  the  urine.  In  some  of  my  other  cases,  the  same  result, 
though  in  a  less  degree,  was  noted. 

Effects  of  too  large  a  dose. — In  cases  of  myxcedema  and  sporadic 
cretinism,  large  doses  are  very  apt  to  produce  acute  thyroidism — 
profound  gastro-intestinal  disturbance  (furred  tongue,  vomiting, 
diarrhoea,  pain  and  tenderness  in  the  epigastric  region),  great 
prostration,  profuse  sweating,  great  and  rapid  loss  of  weight,  rapid 
destruction  of  the  red  blood  corpuscles  (in  one  patient  there  was  a 
loss  of  1,200,000  red  corpuscles  and  \\\  percent,  of  haemoglobin  in 
three  weeks),  severe  myalgic  pains  and  headache,  and  a  feeling  of 
disagreeable  flushing  and  discomfort.  It  is  a  curious  fact  that  in 
one  of  my  cases  (Case  IX.)  the  patient  complained  of  great  pain  in 
the  region  of  the  thyroid  gland.  The  same  fact  was  also  noted  in 
another  case. 

In  some  cases  I  have  observed  an  excited,  hysterical  condition 
produced  by  too  large  doses. 

Effect  of  long-continued  doses. — Whether  the  prolonged   use  of 


MYXCEDEMA.  337 

thyroid  extract  produces  a  deleterious  effect  upon  any  of  the  tissues 
and  organs,  it  is  perhaps,  as  yet,  premature  to  say.  Temporary 
glycosuria  has  been  observed  in  more  than  one  case,  although  no 
example  has  come  under  my  own  observation.  In  one  of  my  cases 
of  myxcedema  (Case  VI.),  the  patient,  after  taking  the  extract  for 
more  than  a  year,  suffered  from  recurring  attacks  of  acute  con- 
gestion of  the  kidney,  with  albuminuria  and  haematuria,  or  rather, 
perhaps,  haematinuria  ;  but  whether  this  was  a  result  of  the  pro- 
longed administration  of  the  thyroid  extract,  I  am  not  prepared 
to  say. 

In  one  case  of  lupus,  the  patient  has  suffered  from  recurring 
attacks  of  syncope,  pain  in  the  stomach  and  retching,  attended  with 
alarming  collapse  and  depression. 

In  Case  XL,  in  which  the  patient  became  extremely  sensitive  to 
the  action  of  the  drug,  acute  tuberculosis  developed.  In  this  case, 
on  several  occasions  a  minute  dose  Q  of  a  tabloid  =  j-^-g  part  of  a 
sheep's  thyroid)  was  administered  without  the  patient's  knowledge. 
Half-an-hour  after  taking  this  small  dose  the  face  became  red  and 
flushed,  the  skin  hot,  the  pulse-rate  perceptibly  increased,  and  the 
temperature  elevated  (from  h  to  I  degree).  This  experiment  was 
repeated  on  different  occasions,  and  always  with  the  same  result. 
During  the  last  two  or  three  months  of  her  illness  the  susceptibility 
to  the  thyroid  was  so  great  that  Dr  Menzies  told  me  that  he  believed 
a  whole  tabloid  (^V  of  a  gland)  would  have  killed  her. 

So  far  as  my  present  experience  enables  me  to  judge,  the  bene- 
ficial effects  of  the  treatment  are  most  pronounced  in  those  cases  in 
which  the  myxcedematous  swelling  is  most  marked.  In  the  atrophic 
■cases,  in  which  there  is  little  or  no  myxcedematous  swelling,  the 
patients  seem  to  be  extremely  susceptible  to  the  action  of  the  drug  ; 
and  in  cases  of  this  kind  the  treatment  appears  to  produce  very 
profound  debility  and  depression.  Cases  XI.  and  XXVII.  illustrate 
this  fact,  and  it  is  interesting  to  note  that  the  facial  appearance  and 
mental  condition  in  both  of  these  cases  was  very  similar — the  face 
was  much  wrinkled,  the  skin  extremely  dry  and  wrinkled,  the 
memory  greatly  impaired,  and  mental  depression  very  marked. 


338  DISEASES   OF   THE   BLOOD   GLANDS. 


Abstract  of  34  Cases  of  Myxcedema  and  of  6  Cases  of 
Sporadic  Cretinism,  Observed  by  the  Author  during 
Life. 

A.— CASES   OF  ADULT  MYXCEDEMA. 

CASE  I. — Typical  Myxcedema  of  Seventeen  Years'  Duration;  Angina  Pectoris ; 
Rapid  Disappearance  of  the  Myxedematous  Swelling  under  Thyroid 
Treatment  j  Sudden  Death  from  Cardiac  Syncope ;  Extreme  Degenera- 
tion of  the  Cardiac  Muscle  and  Atheroma  of  the  Coronary  Arteries. 

Female,  aged  52,  single,  first  seen  as  an  out-patient  at  the  Royal  Infirmary, 
on  2nd  May  1888,  suffering  from  typical  myxcedema,  and  last  on  27th  January 
1893,  after  the  thyroid  treatment  had  been  carried  on  for  four  weeks  by  Dr  John 
Thomson. 

Duration. — 17  years. 

Apparent  cause. — Mental  strain  and  anxiety. 

Present  condition  (2nd  May  1888). — The  case  is  a  highly  typical  one.  The 
swelling  of  the  face,  limbs,  hands,  feet,  and  abdomen  is  marked ;  the  eyelids  are 
swollen  (bags  of  fluid  beneath  the  lower  lids)';  the  skin  of  the  face  is  of  a  sallow 
yellow  hue,  about  the  eyelids  it  is  waxy  and  translucent ;  the  lips  are  purple, 
but  not  swo//en ;  the  nose,  too,  is  not  flattened  and  broadened  as  it  is  in  most 
cases  of  myxcedema  ;  a  well-marked  blush  is  present  on  each  cheek,  and  also 
over  the  nose  ;  the  hair  of  the  head  is  scanty ;  the  scalp  is  encrusted ;  the 
eyebrows  are  wanting  ;  the  tongue  is  large  and  flabby ;  the  hands  and  feet  are 
markedly  enlarged  ;  supraclavicular  swellings  are  well  marked.  The  patient 
states  that  she  never  sweats.  She  always  feels  cold  ;  even  on  the  hottest 
summer  day  she  never  can  get  warm  ;  she  much  dislikes  taking  a  drink  of  cold 
water.  Her  speech  is  typically  slow,  monotonous,  and  thick.  The  thyroid 
gland  cannot  be  felt.  Eyesight  and  hearing  are  impaired.  The  movements 
and  gait  are  characteristically  slow  and  deliberate.  Muscular  feebleness  is  a 
very  marked  feature  of  the  case.  The  patient  says  that  she  sleeps  badly.  Her 
memory  is  impaired  ;  all  her  intellectual  processes  seem  to  be  carried  on  slowly. 
The  urine,  which  has  a  specific  gravity  of  1015,  does  not  contain  albumen. 
The  temperature  is  subnormal.  The  appetite  is  bad,  the  bowels  constipated. 
The  patient  occasionally  suffers  from  palpitation,  and  when  she  was  able  to  go 
about  more  actively  she  used  to  feel  short  of  breath  on  exertion.  The  first 
sound  of  the  heart,  as  heard  at  the  apex,  is  feeble,  but  there  is  no  evidence  of 
valvular  disease.  The  heart  is  not  enlarged,  nor  is  the  aortic  second  sound 
accentuated.  The  pulse  tension  is  not  increased ;  the  pulse  numbers  70  per 
minute.     There  is  no  ordinary  cedema  of  the  feet. 

After  this  date,  May  1888,  I  had,  through  Dr  John  Thomson's  kindness,  the 
opportunity  of  seeing  the  patient  from  time  to  time. 

Noteworthy  and  exceptional  symptoms.  —  In  August  1892,  she  had  a  severe 
and  typical  attack  of  angina  pectoris,  and  from  August  1892  until  22nd  December 
1892  (when  the  thyroid  treatment  was  commenced)  several  attacks,  though  less 
severe,  of  a  similar  kind. 

Thyroid  treatment  commenced  22nd  December  1892. 

Preparation  and  Dose. — Raw  gland  Q  twice  a  week),  increased  on  31st 
December  to  l  gland  twice  a  week. 

Ultimate  results  of  treatment.—  On  6th  January  1893,  patient  complained 


MYXCEDEMA.  339 

of  severe  angina-like  pain,  produced  by  over-exertion.  Nitro-glycerine  pre- 
scribed. 

On  12th  January ',  thyroid  stopped,  and  ordered  to  remain  in  bed. 

On  ijth  January,  the  myxcedematous  symptoms  had  almost  disappeared  ; 
patient  was  very  weak,  complaining  of  epigastric  pain. 

On  27th  January  I  saw  her  with  Dr  John  Thomson  and  it  was  agreed  to 
continue  the  digitalis,  peptonised  milk,  and  whisky  which  she  had  been  taking. 

At  9.30  the  same  evening,  the  patient,  against  express  orders  to  the  contrary, 
got  up  for  the  purpose  of  having  her  bed  made,  complained  of  feeling  faint  and 
died  suddenly  from  cardiac  syncope. 

Post-mortem  29th  January  1893.  —  Thyroid  gland  markedly  atrophied; 
pituitary  enlarged ;  kidneys  healthy.  The  heart  was  very  flabby ;  the  left 
ventricle  dilated ;  its  walls  in  an  extreme  state  of  degeneration,  especially 
towards  the  apex,  where  the  muscular  tissue  appeared  to  be  entirely  replaced 
by  a  greenish-yellow  looking  material.  The  base  of  the  aorta  was  studded  with 
patches  of  atheroma,  and  the  orifices  of  the  coronary  arteries  were  markedly 
narrowed.  Both  coronary  arteries  were  atherosed,  but  no  distinct  clot  was 
detected  in  the  branch  going  to  the  degenerated  portion  of  the  left  ventricle 
and  to  the  septum. 

Dr  Gordon  Sanders  kindly  undertook  the  microscopical  examination,  which 
showed  that  the  heart  muscle  was  in  an  advanced  state  of  degeneration. 

Remarks. — In  this  case,  death  resulted  from  sudden  cardiac  failure,  and  was 
undoubtedly  due  to  the  extremely  degenerated  condition  of  the  heart  muscle. 
The  cardiac  weakness  was  doubtless  increased  by  the  thyroid  treatment, 
notwithstanding  the  fact  that  the  thyroid  extract  had  been  stopped  more  than  a 
fortnight  before  the  patient's  death,  and  the  total  dose  of  thyroid  which  was 
administered  (2J  sheep's  thyroids  in  the  course  of  three  weeks)  was  small. 
Nevertheless  it  had  a  very  marked  effect  on  the  myxcedematous  condition  ; 
indeed,  it  may  be  stated  that,  so  far  as  the  myxcedematous  symptoms  were 
concerned,  the  treatment  was  eminently  satisfactory. 

The  case  shows  the  extreme  importance  of  giving  small  doses  of  the  remedy 
in  all  cases  in  which  there  is  reason  to  suspect  any  degeneration  of  the 
cardiac  muscle,  and  of  rigidly  avoiding  all  causes  of  cardiac  syncope  in  cases 
in  which  marked  cardiac  feebleness  and  debility  are  produced  as  the  result  of 
the  thyroid  treatment.  Though  express  directions  to  the  contrary  were  given, 
the  patient  was,  on  the  evening  of  the  27th  January,  injudiciously  taken  out  of 
bed  and  allowed  to  sit  up  while  her  bed  was  being  made.  Immediately  she  got 
into  the  erect  position  she  complained  of  feeling  faint,  and  dropped  down  dead. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  192; 
and  in  "Atlas  of  Clinical  Medicine,"  Vol.  i.,  p.  15  (See  Plate  III.). 

CASE  II. — Typical  Myxcedema  and  Right-sided  Hemiplegia.  No  Thyroid 
Treatment. 

Male,  aged  59,  turner,  seen  as  an  out-patient  at  the  Edinburgh  Royal 
Infirmary  on  1st  July  1889. 

Duration. — 5  years. 

Apparent  cause. — None. 

Present  condition. — The  patient  complains  of  weakness  and  a  sensation  of 
coldness  ;  the  body  is  bulky  ;  the  face  moon-shaped,  swollen  under  the  eyes, 
and  of  a  dingy  yellow  colour ;  there  is  no  pink  blush  on  the  cheeks ;  the  tongue 
is  very  large  ;  the  hands  and  feet  broad ;  the  abdomen  large  ;  the  speech  is 


34-0  DISEASES   OF   THE   BLOOD   GLANDS. 

charactistically  thick  ;  the  hair  very  thin  ;  the  scalp  encrusted  ;  the  skin  dry 
and  harsh  ;  the  patient  does  not  sweat  ;  the  temperature  subnormal  ;  the 
memory  impaired;  the  patient  sleeps  well;  the  appetite  is  impaired;  the 
bowels  constipated.  The  pulse  is  slow  (60);  the  aortic  second  sound  is 
accentuated;  the  mucous  membranes  are  somewhat  anaemic;  there  is  no 
albumen  in  the  urine.  The  thyroid  gland  cannot  be  felt. 
Result. — Not  known. 

CASE  III. — Advanced  and  Typical  Myxoedema  of  Twenty-four  Years'  Stand- 
ing; Atheroma  of  the  Superficial  Vessels ;  Disappearance  of  the  Myxcede- 
matous  Symptoms  ttnder   Thyroid  Treatment ;  Return  of  Mental  and 
Bodily  Activity;  Severe  Attack  of  Influenza  Two  Years  Subsequently ; 
Recovery. 
Female,  aged  63,  widow,  six  children,  was  first  seen  as  an  out-patient  at  the 
Edinburgh  Royal  Infirmary,  9th  July  1890,  and  was  admitted  as  an  in-patient 
on  19th  January  1893,  suffering  from  typical  and  very  advanced  myxcedema. 
Duration. — 23  or  24  years. 
Apparent  cause. — None. 

Condition  on  admission. — The  patient  complained  of  great  debility,  of  loss 
of  memory  ;  failure  of  sight  and  hearing  ;  and  of  great  sensibility  to  cold.  The 
features  were  broad  and  coarse ;  the  face  was  markedly  swollen,  the  skin  of  the 
face  of  a  sallow  yellow  colour;  the  lips  were  swollen,  the  lower  lip  in  particular 
being  large,  swollen,  elastic-feeling,  and  to  some  extent  pendulous  and  everted ; 
the  eyelids  were  markedly  swollen,  a  bag  of  fluid  being  present  beneath  each 
lower  lid  ;  a  well  marked  capillary  blush  was  present  on  each  cheek ;  the 
scalp  was  almost  destitute  of  hair,  and  thickly  covered  with  dirty  brown 
scabs  or  crusts ;  the  eyebrows  were  wanting,  and  the  eyelashes  had  for  the 
most  part  disappeared ;  the  eyebrows  were  elevated ;  the  forehead  transversely 
wrinkled.  At  this  date  the  baldness  was  much  more  marked  than  at  the  time 
when  the  painting  which  I  have  reproduced  elsewhere  ("Atlas  of  Clinical 
Medicine,"  Plate  I.)  was  made.  The  body  generally  was  large  and  swollen;  the 
hands  and  feet  broad  and  flat.  Large  elastic  swellings  were  present  above  the 
clavicles  ;  the  thyroid  gland  could  not  be  felt.  The  skin  was  dry  and  harsh, 
and  the  patient  never  sweated.  The  temperature  was  subnormal  (970  to  97°. 4 
Fahr.).  The  speech  was  slow  and  thick.  The  patient  was  so  weak  and  feeble 
that  she  could  hardly  walk.  The  memory  and  mental  power  were  markedly 
impaired  ;  sight  and  hearing  were  defective.  The  patient  slept  well.  The 
appetite  was  poor,  the  tongue  furred,  the  bowels  always  constipated.  The 
urine  was  pale,  sp.  gr.  1.014;  it  deposited  some  mucus,  but  did  not  contain 
albumen.  (In  1890,  when  the  patient  first  came  under  my  notice,  a  small 
quantity  of  albumen  was  present.)  The  superficial  vessels  were  atheromatous, 
and  the  heart's  action  and  impulse  were  weak;  the  pulse  was  rather  slow  (60) ; 
the  patient  was  anaemic  ;  red  corpuscles  numbered  3,320,000  ;  hemoglobin  = 
70  per  cent.  ;  the  feet  were  swollen  at  night. 

Noteworthy  and  exceptional  symptoms. — Buzzing  in  head;  superficial  vessels 
atheromatous;  sight  and  hearing  much  impaired. 

Thyroid  treatment  commenced  on  25th  January  1893. 

Preparation  and  Dose. — At  first  the  raw  gland  Oith),  subsequently  B.  &  M. 
liquid  extract  (5-7  drops).     Strychnine  and  strophanthus. 

Immediate    results    of    treatment. — Disappearance   of  the   myxcedematous 
symptoms,  sweating,  desquamation  of  the  skin,  rise  in  temperature  and  pulse, 


MYXCEDEMA.  34 1 

growth  of  hair,  etc.,  great  improvement  in  strength,  mental  power,  hearing,  and 
seeing.     Fainted  twice  on  getting  out  of  bed  during  the  course  of  treatment. 

Discharged  17  th  May,  wonderfully  well. 

Subsequent  progress  of  the  case. — During  1893  (and  subsequently)  the 
patient  did  her  housework  (previously  she  had  not  been  able  to  do  anything 
for  years). 

In  January  1895,  had  a  severe  attack  of  influenza  and  pneumonia,  was 
unconscious  for  2  or  3  days,  but  recovered  (a  remarkable  fact  in  a  woman  of 
68  with  atheromatous  arteries  and  a  feeble  heart,  who  had  been  myxcedematous 
for  25  or  26  years) ;  was  in  bed  for  6  weeks.     Has  since  been  well. 

On  14th  May  1895,  shown  to  students  at  my  clinique,  looked  at  least  10 
years  younger  than  her  age,  whereas  before  thyroid  treatment  commenced 
(in  January  1893)  looked  several  years  older  than  her  age;  hair  of  head  black 
in  colour,  hardly  a  grey  hair  amongst  it  and  nearly  a  foot  in  length  (before 
treatment  almost  bald);  memory  very  good;  doing  all  her  housework.  Is 
taking  5  grains  of  dried  extract  daily. 

Seen  8th  April  1898. — Looking  remarkably  well  and  not  her  age  (70  last 
August).  Says  on  the  whole  she  feels  very  well,  though  she  has  had  several 
slight  attacks  of  influenza  during  the  past  four  years.  She  continues  able  to  do 
light  housework.  There  is  still  a  little  puffiness  about  the  eyelids,  but  no 
evidence  of  myxcedematous  swelling ;  the  lips  are  thin,  the  tongue  not  enlarged  ; 
the  speech  is  quite  sharp;  memory  and  mental  power  very  active;  does  not 
feel  the  cold  at  all,  in  fact  face  frequently  flushes  up  especially  on  the  least 
excitement  or  agitation;  skin  moist,  sweats  naturally,  hair  still  growing  thick, 
beginning  to  get  grey.  Her  left  eye  is  now  quite  blind  (cataract).  She  con- 
tinues to  take  the  thyroid,  gr.  v.,  every  day  or  every  other  day.  She  once  left  it 
off  for  3  months,  but  had  to  begin  it  again  as  all  the  old  symptoms  began  to 
return  (weakness,  swelling,  feeling  of  cold,  etc.). 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  134  ;  and 
in  "Atlas  of  Clinical  Medicine,"  Vol.  i.,  page  13,  where  it  is  represented  in 
Plate  I. 

CASE  IV. — Typical  Myxcedema;  Disappearance  of  all  the  Symptoms  under 
Thyroid  Treatment. 

Female,  aged  26,  single,  seen  26th  January  1891,  suffering  from  typical 
myxcedema. 

Duration. — 4  years. 

Apparent  cause. — None. 

Present  condition. — The  patient  complained  of  debility,  and  she  was  some- 
what anaemic.  The  eyelids,  face,  legs,  abdomen,  and  body  generally  swollen. 
The  face  was  of  a  dingy,  yellow  colour  ;  a  pink  blush  was  present  on  each 
cheek.  The  mouth  was  broad  and  large  ;  the  lips  were  thick,  elastic,  and  bluish 
in  colour ;  the  hair  very  scanty.  The  patient  stated  that  she  had  not  a  third  of 
the  hair  she  had  a  few  years  previously.  The  colour  of  the  hair  has  changed  ; 
it  was,  she  said,  less  golden  than  it  used  to  be.  Elastic  swellings  were  present 
above  the  clavicles  ;  the  thyroid  gland  could  not  be  felt.  The  skin  was  dry  and 
harsh,  and  the  secretion  of  sweat,  which  used  to  be  very  profuse,  almost 
entirely  arrested.  Several  warts  had  developed  on  the  skin  during  the  past 
three  years.  The  voice  was  rougher  and  harsher  than  it  used  to  be  ;  the 
articulation  was  thick ;  the  buccal  mucous  membrane  was  swollen  ;  the  whole 
appearance  of  the  patient  heavy  and  stolid.     The  hands  were  much  larger,  and 


342  DISEASES   OF   THE   BLOOD   GLANDS. 

the  fingers  much  more  swollen  than  they  used  to  be.  The  patient  stated  that 
she  felt  quite  a  different  person  in  warm  weather ;  in  cold  weather  she  seems 
unable  to  think  or  exert  herself.  The  tongue  was  large.  The  memory  was 
impaired  ;  the  patient  sleeps  well.  The  thyroid  gland  could  not  be  felt.  The 
appetite  was  poor ;  the  digestion  bad  ;  the  bowels  constipated.  The  tem- 
perature was  subnormal  (97°.6),  the  pulse  small  and  weak,  68  per  minute  ;  the 
heart's  action  and  sounds  feeble.  The  urine  was  free  from  albumen.  The 
menstruation  was  irregular. 

Soon  after  this  date  the  patient  consulted  me  as  to  the  advisability  of  going 
to  Barbados.  I  advised  her  to  do  so,  thinking  that  the  warm  climate  would 
be  beneficial. 

Noteworthy  and  exceptional  features. — Her  uncle  died  from  myxcedema. 
Colour  of  hair  changed — it  became  less  golden  with  the  development  of  the 
disease. 

Thyroid  treatment  commenced  in  Barbados,  January  1892. 

Preparation  and  Dose. — Raw  gland. 

Immediate  results  of  treatment. — Rapid  disappearance  of  all  the  myxce- 
dematous  symptoms. 

Subsequent  progress.  — I  saw  the  patient  on  4th  September  1893,  and  did 
not  know  her.  She  then  told  me  that  the  sea  air  and  damp  had  a  most 
depressing  effect  upon  her,  and  that  too  large  a  dose  of  the  thyroid  produced  a 
severe  aching  pain  like  toothache  in  the  left  arm. 

In  February  1898,  I  met  her  in  the  street  and  did  not  know  her  ;  looks 
several  years  younger  than  she  used  to  do  and  her  facial  appearance  quite 
altered. 

On  7th  April  1898,  she  wrote  me  :  "  It  will  be  three  years  next  month  since 
I  left  Barbados.  During  that  time  the  greatest  progress  has  been  in  nerve- 
strength.  I  am  in  every  way  less  nervous,  do  not  suffer  such  acute  pain  from 
any  slight  injury,  am  not  so  easily  excited,  and  therefore  less  liable  to  nervous 
headache.  In  fact  I  fancy  I  am  stronger  nervously  than  I  have  been  since  I 
was  a  young  girl.  It  is  very  seldom  now  that  I  have  the  old  severe  attacks  of 
pain,  but  when  they  do  come,  I  notice  a  marked  difference  in  the  way  I  revive 
after  them,  instead  of  being  almost  prostrated  with  exhaustion.  I  still  have  a 
great  shrinking  from  cold,  and  am  particularly  sensitive  to  changes  of  sunshine. 
I  am  sometimes  ashamed  to  feel  and  look  really  ill  on  a  dull  cold  day,  and  next 
day — if  the  sun  comes  out— be  quite  well  again  !  This  sensitiveness  to  cold 
seems  to  have  affected  my  head  a  good  deal.  Three  times  since  returning  to 
Scotland  I  have  had  long  spells  of  a  dull  headache,  the  first  one  (December 
1895)  lasting  nearly  two  months.  In  general  health  I  am  really  well — probably 
as  strong  as,  and  I  think  more  steadily  strong  than,  I  was  at  17.  I  have  lost 
the  intense  exuberant  joy  in  living  which  astonished  my  Barbados  friends  so 
much,  but  it  may  have  been  partly  due  to  my  nervous  condition,  and  might  not 
return  even  if  I  went  back  to  the  heat  and  sunshine  to-morrow.  The  only  real 
traces  of  illness  left  are  a  constant  tendency  to  indigestion,  and  a  slight 
weakness  of  memory.  The  latter,  however,  is  strengthening,  and  I  begin 
to  depend  on  my  memory  in  teaching  in  a  way  which  rive  years  ago  I 
should  not  have  dreamt  would  have  been  possible.  The  oddest  thing  about 
my  digestion  is  the  way  medicines  disagree  with  me — frequently  producing 
violent  results,  and  occasionally  acting  in  quite  an  opposite  fashion  from 
that  intended.  I  have  a  horror  of  trying  any  remedy  now,  and  the  only 
thing   reliable   for    indigestion,    or   as    an    aperient,    is    whisky  and    water ! — 


MYXCEDEMA.  343 

and  that,  as  a  strong  total  abstainer,  I  dislike  taking.  To  keep  myself  well 
I  depend  on  the  thyroid  and  hot  baths.  For  the  last  year  and  a  half,  half  a 
tabloid  (  =  2-0-  grs.)  of  thyroid  has  been  enough.  I  have  sometimes  tried  doing 
without  the  thyroid  for  a  day  or  two,  but  always  by  the  second  day  weariness 
and  headache  have  set  in.  Regular  warm  bathing  helps  me  greatly.  I  take  a 
hot  bath  on  an  average  every  second  morning,  and  once  in  two  or  three  weeks 
have  a  '  Russian  (steam)  bath.'  I  greatly  enjoy  exercise  —  particularly  very 
rapid  motion.  I  cannot  afford  to  keep  up  my  horseback-riding,  but  I  cycle  a 
great  deal,  and  enjoy  dancing  like  a  girl  of  15!  In  fact  those  years  of  illness 
seem  to  have  been  in  a  way  missed  out  of  my  life,  and  in  many  ways  I  fancy  I 
act  and  feel  more  like  25  than  33  ! 

"  I  hope  I  have  told  you  what  you  wish  to  know.  If  not,  I  shall  be  most 
happy  to  answer  any  special  questions,  as  I  owe  you  a  great  debt  of  gratitude 
for  your  help  and  kindness  during  a  terribly  dark  time  of  my  life." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  167. 


CASE  V. —  Typical  Myxoedema ;  Rapid  Disappearance  of  All  the  Symptoms 
under  Thyroid  Treatment. 

Female,  aged  41,  married,  one  child,  seen  in  consultation  28th  May  1891, 
suffering  from  typical  myxcedema. 

Duration. — 4  years. 

Apparent  cause. — None. 

Present  condition. — The  patient  complained  of  great  bodily  weakness,  and 
of  loss  of  memory  and  mental  power.  The  face  and  body  were  swollen,  but 
the  hands  and  feet  were  not  characteristically  misshapen.  The  eyelids  were 
swollen,  the  lips  thick  and  elastic-feeling,  the  hair  of  the  head  and  eyebrows 
scanty,  the  scalp  dry  and  rough.  A  pink  blush  was  present  on  each  cheek  ; 
several  large  brown  pigmented  patches  were  present  on  the  forehead,  and  the 
skin  of  the  neck  was  of  a  dingy  yellow  colour.  The  tongue  and  uvula  were 
swollen  ;  the  speech  was  markedly  thick,  and  the  voice  rough  and  hoarse. 
The  skin  was  dry;  the  patient  stated  that  she  perspired  much  less  than  she 
used  to  do;  the  temperature  was  subnormal  (960  Fahr.)';  she  was  very  sensitive 
to  cold.  Elastic  swellings  were  present  above  the  clavicles.  The  thyroid  gland 
could  not  be  felt.  The  heart's  action  and  pulse  were  very  feeble,  the  aortic 
second  sound  accentuated;  the  pulse  numbered  yo  per  minute;  the  patient 
was  somewhat  anaemic,  and  was  subject  to  fainting  attacks,  and  quite  unable  to 
undergo  any  exertion  either  of  body  or  mind  ;  the  memory  was  impaired;  the 
patient  slept  well  ;  the  menstruation,  when  the  patient  was  first  seen,  regular, 
subsequently  arrested.  The  urine  was  free  from  albumen,  and  there  was  no 
visceral  disease.  The  appetite  was  poor;  she  was  subject  to  attacks  of  diarrhoea, 
which  came  on  without  any  obvious  cause. 

Various  remedies  were  from  time  to  time  employed,  but  without  anv  distinct 
benefit. 

There  is  nothing  of  importance  to  note  between  May  1891  and  February 
1893,  except  that  during  the  winter  of  1892-93  "the  advent  of  frost"  (so  her 
husband  wrote  me  on  13th  February  1893)  "caused  her  to  rally  to  such  a  degree 
that  she  went  out,  and  enjoyed  herself  immensely  when  everybody  felt  the 
intense  cold  to  be  slightly  inconvenient."  He  added:  "In  this  connection  I 
may  mention  that  she  rarely  has  cold  limbs  or  feet  now.  There  is  a  great 
change  for  the  better  in  this  respect." 


344  DISEASES   OF   THE   BLOOD   GLANDS. 

Noteworthy  and  exceptional  symptoms. —  Hands  and  feet  not  swollen; 
occasional  causeless  diarrhoea;  during  1892  (when  the  symptoms  were  all 
well  marked  and  before  the  thyroid  treatment  had  been  commenced)  she 
enjoyed  the  cold. 

Thyroid  treatment  commenced  9th  February  1893. 

Preparation  and  Dose. — Liquid  extract  3L  daily  (D.  &  F.'s)— equal  to  ^th  of 
a  gland — every  other  day. 

Immediate  result  of  treatment.— After  four  doses,  a  distinct  improvement; 
in  the  course  of  a  month  her  husband  wrote  :  "  Her  bodily  health  and  spirits 
have  undergone  such  a  change  that  she  appears  to  be  another  creature.  She 
is  much  thinner,  and  more  healthy  looking.  The  thyroid  extract  appears  to  be 
the  veritable  Elixir  vita  /"  In  the  course  of  two  months,  the  myxcedematous 
symptoms  had  completely  disappeared ;  the  hair  was  growing ;  the  menstrua- 
tion (absent  for  several  months  previously)  had  returned. 

Subsequent  progress. — In  August  1893  (6  months  after  the  commencement 
of  the  treatment)  she  ascended  the  highest  of  the  Ochils  (1700  feet) ;  she  was 
the  least  distressed  and  fatigued  of  the  party,  when  they  returned  home  in  the 
evening.  In  October  1893,  her  hair,  which  before  the  commencement  of  the 
treatment  was  very  scanty,  was  most  luxuriant.  She  has  continued  in  perfect 
health  ever  since. 

On  2nd  April  1898,  when  last  seen,  she  looked  the  picture  of  health  ;  con- 
tinues to  take  the  thyroid,  as  a  rule,  every  third  or  fourth  day,  sometimes  at 
longer  intervals  ;  always  finds  she  must  return  to  it  again. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  164. 

CASE  VI. —  Typical  and  Advanced  Myxcedema;  Complete  Disappearance  of  the 
Myxcedematous  Symptoms  under  Thyroid  Treatment. 

Female,  aged  40,  married,  no  children,  seen  on  23rd  September  1891. 

Duration. — 2  years  or  more. 

Apparent  cause. — None,  unless  mental  anxiety,  of  which  she  has  had  a  great 
deal.  Had  typhoid  fever  at  the  age  of  18,  and  says  she  has  never  been  so  strong 
since. 

Present  condition. — Patient  complains  of  debility  and  muscular  feebleness  ; 
body  bulky;  face  markedly  swollen,  of  a  dingy  yellow  colour  ;  baggy  swellings 
of  lower  eyelids  ;  pink  blush  on  the  cheeks  ;  speech  characteristic  ;  tongue  and 
throat  swollen  ;  some  difficulty  in  swallowing  ;  says  the  tongue  gets  very  tired  if 
she  attempts  to  speak  much,  and  if  she  is  at  all  nervous  can  scarcely  manage  to 
swallow  ;  fatty  swellings  above  the  clavicles  ;  hands  spade-like  ;  feet  broad  and 
thick  ;  used  to  have  hot  hands  and  feet,  now  always  feels  cold  ;  temperature 
subnormal  ;  skin  dry,  never  sweats,  but  never  did  sweat  much  ;  hair  thin  and 
dry;  scalp  scaly;  nails  brittle  ;  speech  thick  ;  appetite  poor  ;  bowels  constipated  ; 
goes  to  bed  feeling  thoroughly  exhausted  ;  memory  bad,  has  not  noticed  that  it 
was  worse  in  cold  weather  ;  thinks  slowly ;  sleeps  well,  but  has  most  distressing 
dreams  ;  complains  much  of  headache  and  "  thudding  "  noises  at  the  back  of  the 
head  ;  distinctly  anaemic  ;  optic  discs  natural  ;  menstruation  scanty,  has  never 
had  monorrhagia  ;  the  thyroid  gland  cannot  be  felt  ;  pulse  60  ;  urine  normal. 

Treatment. — The  patient  was  treated,  first,  by  the  subcutaneous  injection  of 
thyroid  extract,  and  subsequently,  by  the  administration  of  the  dried  extract  by 
the  mouth. 

Result. — Dr  Robertson  Crease  of  South  Shields,  who  prescribed  and  con- 
ducted the  treatment,  wrote  me  on  8th  April  1898  as  follows  : — "  For  two  years 


MYXCEDEMA.  345 

after  you  saw  her  I  injected  twice  weekly  15  m.  thyroid  extract;  after  that  period 
she  continued  to  take  the  thyroid  tabloids  twice  daily.  This  treatment  held  her 
disease  in  check  partly.  She  lost  her  husband  18  months  ago,  and  had  much 
family  care  and  anxiety.  The  myxcedematous  symptoms  then  returned,  in  spite 
of  three  doses  (tabloids)  per  day.  I  was  again  asked  to  see  her,  and  at  her  own 
request  I  began  the  thyroid  extract  injections,  15  m.  twice  a  week.  After  five 
injections,  the  change  in  her  appearance  was  marked — the  skin  is  less  dry  and 
harsh ;  the  temperature  has  risen  ;  the  flow  of  saliva  has  ceased  ;  she  says  that 
she  feels  lighter ;  her  spirits  are  better.  I  propose  to  give  one  injection  per  week 
and  two  tabloids  per  day.  She  has  little  faith  in  the  tabloids  ;  but  she  has  great 
confidence  in  the  injections." 

CASE  VII. —  Typical  and  Advanced  Myxcedema  ;  Death  ;  No  Thyroid  Treat- 
ment. 

Female,  aged  42,  married,  eight  children,  seen  19th  October  1891,  suffering 
from  all  the  characteristic  symptoms  of  typical  and  advanced  myxcedema. 

Duration. — 2  years. 

Apparent  cause. — A  severe  illness,  the  exact  nature  of  which  I  was  unable 
to  ascertain,  seems  to  have  preceded  the  development  of  the  myxcedematous 
symptoms.     Has  suffered  from  menorrhagia  since  the  birth  of  her  last  child. 

Symptoms. — Complains  of  great  weakness  and  giddiness  ;  says  she  cannot 
get  the  limbs  to  work,  cannot  get  them  to  move  sharply.  The  body  as  a  whole 
is  bulky  ;  the  face  is  full  ;  the  eyelids  are  swollen  and  translucent-looking  ;  the 
skin  of  the  face  is  of  a  dingy  yellow  colour  ;  a  pink  blush  is  present  on  the 
cheeks  ;  the  lips  are  swollen  and  blue  ;  the  nose,  cheeks  and  hands  are  also 
somewhat  blue ;  the  ears  are  large ;  large  elastic  swellings  are  present  above  the 
clavicles  ;  the  hands  and  feet  are  broad  and  thick  ;  the  abdomen  is  large  and 
pendulous  ;  the  under-surface  of  the  tongue  is  swollen ;  the  speech  is  character- 
istically thick;  the  throat  is  not  swollen,  but  the  buccal  mucous  membrane  is 
anaemic  ;  the  eyebrows  are  scanty  and  ragged ;  the  scalp  is  almost  destitute  of 
hair  and  thickly  encrusted ;  the  patient  feels  the  cold  very  much  ;  the  tempera- 
ture is  subnormal  ;  she  does  not  feel  sure  that  she  is  better  in  summer  than  in 
winter  ;  the  skin  is  very  dry  and  rough  ;  for  some  weeks  she  has  experienced  a 
severe  pain  behind  the  knee,  nothing  local  can  be  detected  to  account  for  this  ; 
patient  complains  of  numbness  in  hands  and  feet;  the  knee-jerks  are  exaggerated  ; 
there  is  frequent  headache ;  the  memory  is  impaired  and  the  patient's  mental 
condition  is  peculiar  ;  at  times  she  is  very  irritable,  she  mistakes  people,  some- 
times thinks  her  husband  is  the  nurse  (psychical  blindness);  she  sleeps  badly  ; 
sight  is  quite  good  ;  the  pupils  are  equal  and  active  ;  there  is  no  hemianopsia  ; 
hearing,  taste  and  smell  are  unaffected  ;  the  heart  is  natural  ;  radial  pulse  62, 
small  and  weak  ;  the  appetite  is  good,  digestion  natural,  bowels  regular  ;  the 
urine  is  normal ;  no  thyroid  gland  can  be  felt. 

Treatment. — Warmth  and  tonics  were  prescribed.  As  soon  as  the  thyroid 
treatment  was  introduced,  I  wrote  to  the  patient  advising  her  to  try  it;  and 
learned  from  her  husband  that  she  had  died  a.  short  time  previously. 

CASE  VIII. —  Typical  Myxcedema.     No  Thyroid  Treatment. 

Male,  aged  35,  married,  bookbinder,  seen  as  an  out-patient  at  the  Edinburgh 
Royal  Infirmary  on  22nd  January  1892. 

Duration. — 2  years  or  more. 

Apparent  cause. — None. 


346  DISEASES   OF   THE   BLOOD   GLANDS. 

Present  condition. — The  patient  complains  of  great  lassitude  and  repugnance 
to  exertion  ;  gait  slow  and  ponderous  ;  always  feels  cold;  is  somewhat  anaemic; 
never  sweats;  body  as  a  whole  bulky;  face  swollen  and  of  a  yellowish  tinge; 
no  pink  blush  on  the  cheeks ;  tongue  large ;  throat  swollen ;  hands  spade-like ; 
feet  broad  and  thick ;  abdomen  large ;  no  supraclavicular  swellings ;  hair, 
which  used  to  be  thick  before  the  disease  commenced,  very  scanty,  dry  and 
brittle;  scalp  dirty;  eyebrows  almost  absent ;  memory  defective ;  speech  thick; 
some  difficulty  in  swallowing;  skin  dry  and  rough;  temperature  subnormal 
appetite  poor;  bowels  constipated;  knee-jerks  present;  thyroid  gland  cannot 
be  felt,  the  rings  of  the  trachea  very  distinct.     No  albumen  or  sugar  in  the  urine. 

Subsequent  progress. — Not  known. 

CASE  IX. —  Typical  Myxcedema;  Rapid  Disappearance  of  All  the  Symptoms 
tinder  Thyroid  Feeding  ;  Profuse  Desquamation  of  the  Skin.  Readmis- 
sion  to  Hospital  a  Year  after  Discharge ;  Acute  Bronchitis ;  Albumi- 
nuria; Hematuria  and  Hcematinuria.     Death  Four  Years  Later. 

Female,  aged  48,  widow,  one  child,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  28th  October  1892,  suffering  from  typical  myxcedema. 

Duration. — 5  years. 

Apparent  cause. —  Mental  distress. 

Family  History. — A  step-sister  died  of  phthisis. 

Condition  on  admission. — The  case  was  most  typical,  all  the  characteristic 
symptoms  of  myxcedema  being  present.  The  patient  complained  of  a  feeling 
of  debility,  lassitude,  and  inability  to  exert  herself.  She  always  felt  cold ;  even 
if  she  roasted  herself  before  a  hot  fire,  she  could  not  get  heated  up.  She  stated 
that  she  was  always  worst  in  the  winter  and  cold  weather.  The  body  as  a 
whole  was  bulky;  the  movements  heavy  and  clumsy;  the  abdomen  large  and 
pendulous.  The  face  was  moon-shaped,  swollen  and  puffy,  of  a  tawny-yellow 
colour,  except  about  the  eyelids,  where  it  had  the  pale,  transparent,  waxy 
appearance  which  is  so  characteristic  of  the  disease.  A  well-marked  pink 
blush  was  present  on  each  cheek.  The  lips  were  thick;  the  eyelids  were 
swollen;  the  hair  was  scanty;  the  scalp  dirty,  and  encrusted  with  brown  scales 
and  crusts;  the  hands  were  "spade-shaped";  the  feet  broad  and  thick.  The 
speech  was  thick  and  drawling,  as  if  the  patient  had  something  in  the  mouth  or 
throat.  The  tongue  was  large  and  flabby;  the  throat  was  swollen.  She  stated 
that  saliva  used  frequently  to  flow  out  of  her  mouth,  especially  during  the 
night;  and  that  her  nose  often  ran,  without  any  cold  or  other  apparent  cause. 
Elastic  swellings  were  present  above  the  clavicles.  The  skin  was  harsh  and 
dry;  she  never  sweated,  though  the  palms  of  the  hands  were  at  times  moist. 
The  pulse  was  slow ;  it  varied  from  40  to  50  in  the  minute,  the  average  being 
46.  The  temperature  was  always  subnormal  (average,  97°  Fahr.).  The  respira- 
tions averaged  14  per  minute.  The  urine  contained  a  distinct  trace  of  globulin, 
but  no  serum  albumen.  The  memory  and  mental  activity  were  much  impaired. 
The  patient  stated  that  she  felt  it  an  effort  to  think;  at  the  same  time  she 
added  that  she  was  more  easily  agitated  than  she  used  to  be ;  she  slept  well. 
The  appetite  was  good;  she  had  not  had  any  indigestion  for  two  months;  the 
bowels  were  constipated.  The  red  blood  corpuscles  numbered  3,820,000  per 
0. mm.,  and  the  ha-inojjlobin  amounted  to  65  percent.  The  weight  was  11  st. 
4^  lbs. 

Noteworthy  symptoms. — The  urine  contained  a  distinct  trace  of  globulin, 
but  no  serum   albumen.     Menstruation,  which  had  been  arrested  for  several 


MYXCEDEMA.  347 

months,  returned  immediately  under  thyroid  treatment,  and  the  urine  contained 
an  excessive  quantity  of  mucus. 

Thyroid  treatment  commenced  on  8th  November  1892. 

Preparation  and  Dose. — Raw  gland  ;  at  first  half  a  gland  daily,  subsequently 
smaller  doses. 

Immediate  result. — The  production  of  acute  thyroidism  (severe  headache, 
pain  in  the  position  of  the  thyroid,  in  the  back  and  limbs,  anorexia,  pain  in 
stomach,  vomiting,  diarrhoea,  thickly  furred  tongue),  rise  in  temperature  and 
pulse,  profuse  sweating,  menstrual  flow  which  had  been  arrested  for  8  months, 
diminution  of  red  blood  corpuscles  and  haemoglobin  (from  3,820,000  and  65  % 
to  2,620,000  and  54  7o)>  the  rapid  disappearance  of  the  myxcedematous  swelling, 
loss  of  185  lbs.  in  weight,  the  profuse  discharge  of  a  very  large  quantity  of 
mucus  in  the  urine,  disappearance  of  globulin. 

Subsequently. — Growth  of  hair,  profuse  desquamation  of  the  skin  which 
became  quite  soft  and  natural,  increase  of  red  blood  corpuscles  and  haemoglobin 
(from  2,620,000  and  54  %  to  4,310,000  and  70  °/o)>  restoration  of  strength,  etc. 

Weight  on  admission  11  st.  4^  lbs.;  on  discharge  10  st.  12  lbs. 

The  patient  was  discharged  from  hospital  on  18th  February  1893,  saying 
that  she  felt  quite  well  and  "equal  to  anything."  The  change  in  her  appear- 
ance was  so  great  that  her  daughter  said  when  she  saw  her,  "  I  did  not  recog- 
nise her  face ;  I  saw  that  her  body  was  the  same,  but  her  face  was  so  much 
changed  I  did  not  know  her." 

Subsequent  progress  of  the  case. — Patient  who  had  not  been  able  to  do  any 
work  for  5  years,  worked  during  the  summer  of  1893. 

I?i  November  and  December  1893,  had  several  attacks  of  bleeding  from  the 
kidney. 

On  \%th  February  1894,  was  re-admitted  to  E.R.I.,  suffering  from  bronchitis, 
hematuria,  albuminuria  and  loud  systolic  murmur,  due  to  exposure  to  cold  and 
wet.     Discharged  from  the  E.R.I. ,  urine  normal,  21st  April  1894. 

On  16th  June  1896,  when  I  last  saw  patient,  she  was  keeping  well,  better 
than  for  years  before  the  thyroid  treatment,  but  still  had  a  somewhat  myxce- 
dematous look.  She  was  taking  the  thyroid  (dried  extract)  fairly  regularly. 
The  urine  still  contained  at  times  a  small  quantity  of  albumen. 

On  2jth  May  1898  her  medical  attendant  wrote  me  : — "You  will  be  sorry 
to  hear  that  Jessie  G.  died  last  tueek.  Her  heart  became  very  flabby  and  ceased 
to  respond  to  digitalis,  etc.  She  was  in  very  poor  circumstances  and  refused  to 
go  into  the  poor-house,  and  consequently  received  inadequate  nourishment. 
Four-and-twenty  hours  before  her  death  she  was  affected  with  left  hemiplegia 
(cerebral  haemorrhage)  and  she  was  also  slightly  jaundiced.  The  myxcedematous 
symptoms  were  always  easily  controlled  by  thyroid  extract,  but  when  she  was 
unable  to  obtain  the  remedy  for  any  length  of  time  the  peculiar  symptoms  of 
the  disease  asserted  themselves." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  116. 

CASE  X. — Typical  Myxcedema  ;  Rapid  Disappearance  of  All  the  Symptoms 
under  Thyroid  Treatment. 

Female,  aged  33,  married,  seven  children  and  one  miscarriage,  admitted  to 
the  Edinburgh  Royal  Infirmary  on  26th  December  1892,  suffering  from  typical 
myxcedema. 

Duration. — 3  years. 

Apparent  cause. — Loss  of  blood  last  confinement  and  mental  worry. 


348  DISEASES   OF   THE    I5LOOD    GLANDS. 

Family  History. — A  brother  died  of  diabetes  ;  another  had  swollen  glands. 

Condition  on  admission. —All  the  characteristic  symptoms  of  myxcedema  are 
present.  The  patient  complains  of  debility.  The  body  as  a  whole  is  bulky,  the 
hands  and  feet  are  broad  and  thick  ;  the  face  is  broad,  and  the  lower  lip 
swollen  and  firm  :  the  eyelids  are  swollen.  The  skin  of  the  face  is  of  a 
dingy  yellow  hue  ;  a  pink  blush  is  present  on  the  cheeks  and  nose.  The 
hair  of  the  head  is  very  thin,  the  eyebrows  scanty.  A  pigmented  mole 
has  developed  on  the  right  cheek  since  the  illness  commenced.  A  patch 
of  dry  eczema  is  present  on  the  back  of  the  right  hand  and  wrist.  The 
tongue  and  buccal  mucous  membrane  are  swollen  ;  the  speech  is  slow  and 
thick  ;  the  patient  has  some  difficulty  in  swallowing.  The  skin  is  harsh,  rough, 
and  dry,  except  on  the  face,  where  it  is  smooth.  The  patient  says  that  she 
never  sweats  except  on  the  head  and  forehead,  which  are  occasionally  cold  and 
clammy.  Her  nose  frequently  "runs"  without  any  apparent  cause;  this,  she 
says,  relieves  her  headache,  which  is  often  very  severe.  Since  her  illness  com- 
menced, the  secretion  of  saliva  has,  she  says,  been  more  profuse  than  it  used  to 
be  ;  it  often  runs  from  her  mouth  through  the  night.  She  complains  of  feeling 
cold,  and  of  numbness  in  the  hands  and  feet.  She  says  that  she  always  feels 
better  in  warm  weather.  Her  memory  is  impaired,  and  sight  and  hearing  are 
less  acute  than  they  were  three  years  ago.  Her  gait  is  slow  and  clumsy.  The 
thyroid  gland  cannot  be  felt.  The  temperature  is  subnormal  (970  to  97°.6) ;  the 
pulse  rather  slow  (56  to  68  per  minute)  and  soft.  The  heart's  impulse  is  feeble. 
The  urine  contains  a  small  quantity  of  albumen  (both  serum  albumen  and 
peptone).  The  appetite  is  poor,  the  abdomen  large  (the  result  of  flatulent 
distension),  the  bowels  regular.  The  red  blood  corpuscles  numbered  4,210,000 
per  cubic  millimetre,  and  the  haemoglobin  (estimated  by  Gowers'  instrument)  = 
56  per  cent.  The  menstruation,  which  recommenced  three  months  after  the 
birth  of  the  last  child,  has  since  been  regular,  but  too  profuse. 

Noteworthy  and  exceptional  symptoms. — Frequent  attacks  of  shivering  and 
running  at  eyes  and  nose,  dry  eczema  on  hand,  severe  headaches.  During  the 
treatment,  the  breasts  filled  with  rich  milk. 

Thyroid  treatment  commenced  on  January  1893. 

Preparation  and  Dose. — At  first  the  raw  gland  (ith,  subsequently  increased 
to  ^  and  finally  reduced  to  \  of  a  gland). 

Immediate  results  of  treatment. — Complete  disappearance  of  the  myxe- 
dematous symptoms,  desquamation  of  the  skin,  growth  of  hair  and  complete  cure. 

During  the  course  of  the  treatment,  the  patient  suffered  from  headache,  severe 
myalgic  pains  in  the  back,  chest  and  limbs,  anorexia,  furred  tongue,  sickness, 
vomiting,  epigastric  pain,  diarrhoea  ;  rapid  filling  of  the  breasts  with  rich  milk. 

Was  discharged  from  E.R.I,  on  6th  March  1894,  feeling  quite  well.  Weight 
on  admission  9  st.  6\  lbs.,  on  discharge  9  St.,  greatest  loss  of  weight  during"  the 
treatment  j\  lbs. 

Subsequent  progress  of  the  case. —  Patient  continued  to  take  the  thyroid  and 
continued  well.     Was  confined  in  1894. 

Seen  on  2nd  October  1897  ;  was  then  quite  free  from  myxcedematous  symp- 
toms, and  feeling  strong  and  well  ;  says  she  has  been  very  well  since  she  left 
the  hospital  ;  able  to  do  her  housework  ;  was  confined  3^  years  ago  ;  now 
menstruates  regularly  ;  she  feels  vigorous  and  active  ;  her  speech  is  not  thick  ; 
she  does  not  feel  the  cold  ;  she  sweats  naturally  ;  her  hair  is  as  thick  as  it  ever 
was.     She  continues  to  take  one  gr.  v.  tabloid  night  and  morning. 

Recorded  in  full  in  the  "  Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  129. 


MYXCEDEMA.  349 

CASE  XI. —  Typical  Myxcedema  of  Three  Years'  Duration ;  Intense  Mental 
Depression  ;  Peculiar  Susceptibility  to  tlie  TJiyroid  Extract ;  Disappear- 
ance of  the  Myxedematous  Symptoms  under  Thyroid  Treatment ;  Con- 
tinuation of  the  Bodily  Prostration  and  Mental  Depression  :  Acute 
Tuberculosis ;  Death  a  Year  After  the  Comme7icement  of  the  Thyroid 
Treatment. 

Female,  aged  61,  married,  seven  children  and  one  miscarriage,  seen  in 
consultation  17th  January  1893,  suffering  from  advanced  atrophic  myxcedema  ; 
confined  to  bed  for  several  months. 

Duration. — 3  years. 

Apparent  cause. — None. 

Present  condition. — The  face  was  pale,  and  of  a  dingy  yellow  colour  ;  the 
patient  was  somewhat  anaemic  ;  the  eyelids  and  lower  lips  were  somewhat 
swollen,  but  the  swelling  was  less  marked  than  in  most  typical  cases  of  the 
disease ;  there  was  no  pink  blush  on  the  cheeks  ;  the  hair  was  scanty,  and  the 
scalp  covered  with  dirty  crusts  and  scales  ;  the  skin  was  harsh  and  dry  ;  the 
patient  never  sweated  ;  she  complained  much  of  cold  ;  the  speech  was  thick  ; 
memory,  sight  and  hearing  were  somewhat  impaired  ;  there  was  frequent 
headache  ;  some  numbness  in  hands  and  feet ;  she  occasionally  felt  some 
difficulty  in  swallowing  ;  fatty  swellings  were  present  above  the  clavicles  ;  the 
thyroid  gland  could  not  be  felt.  The  general  state  of  nutrition  was  fairly  good  ; 
the  appetite  poor  ;  the  bowels  constipated.  The  temperature  was  subnormal 
(average  950  to  96°)  ;  the  pulse  60,  and  very  feeble.  The  patient  was  very 
debilitated  ;  mental  depression  was  a  very  marked  symptom.  The  urine  was 
free  from  albumen. 

Noteworthy  and  exceptional  symptoms. — No  pink  blush  on  cheeks,  myxce- 
dematous  swelling  slight,  face  wrinkled,  mental  depression  very  marked,  extreme 
susceptibility  to  thyroid  extract. 

Thyroid  treatment  commenced  18th  January  1893. 

Preparation  and  Dose. — Raw  gland  (J  daily  at  first,  dose  gradually  reduced)  ; 
the  patient  became  extremely  susceptible  to  the  remedy,  until  finally  |th  of  a 
tabloid  =  TTrsth  part  of  a  gland,  once  a  week,  was  too  much. 

Immediate  results  of  treatment. — Rapid  disappearance  of  the  myxcedema, 
growth  of  hair,  but  increase  of  bodily  and  mental  depression. 

Subsequent  progress. — After  some  months,  profuse  sweating  and  diarrhoea, 
pain  in  the  back,  a  feeling  of  heat  and  flushing  all  over  the  body,  a  sensation  as 
if  the  head  would  burst,  a  marked  rise  of  temperature  and  pulse ;  dyspepsia  and 
diarrhoea  resulted  from  the  remedy  even  in  small  doses. 

On  several  occasions,  a  minute  dose  (ith  of  a  tabloid  =  Ti¥th  part  of  a  sheep's 
thyroid  gland)  was  administered  to  the  patient  without  her  knowledge.  Half 
an  hour  after  taking  this  small  dose  the  face  became  red  and  flushed,  the  skin 
hot,  the  pulse-rate  perceptibly  increased,  and  the  temperature  elevated  (from 
\  to  1  degree).  This  experiment  was  repeated  on  different  occasions,  and 
always  with  the  same  result.  During  the  last  two  or  three  months  of  her 
illness  the  susceptibility  of  the  patient  to  the  thyroid  extract  was  so  great  that 
Dr  Menzies  told  me  that  he  believed  a  whole  tabloid  (roth  of  a  gland)  would 
have  killed  her.     The  remedy  had  consequently  to  be  discontinued. 

Acute  phthisis  then  developed  and  patient  died  on  4th  January  1894. 

Post-mortem  examination. — Not  allowed. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,''  Vol.  iii.,  p.  158. 


350  DISEASES   OE   THE   BLOOD   GLANDS. 

CASE  XII. —  Typical  Myxcedema  of  Seven  or  Eight  Years'  Duration,  but  Mental 
Condition  Not  At  All  Impaired;  Rapid  Disappearance  of  All  the  Myxe- 
dematous Symptoms,  and  Complete  Cure  under  Thyroid  Treatment. 

Female,  aged  61,  married,  two  children,  seen  in  consultation  January  1893, 
suffering  from  typical  myxcedema. 

Duration. — 7  or  8  years. 

Apparent  cause. — None. 

Present  condition. — The  body  is  bulky,  the  face  broad,  the  hands  spade-like  ; 
the  feet  broad  and  thick ;  elastic  swellings  are  present  above  the  clavicles ; 
a  well-marked  pink  blush  is  present  on  each  cheek;  the  lips  are  thick,  elastic, 
and  bluish  in  colour;  the  skin  of  the  face  is  of  a  characteristic  dingy  yellow 
colour;  the  hair  is  scanty;  the  skin  is  extremely  rough  and  dry;  the  patient 
never  sweats ;  she  complains  of  always  feeling  cold ;  the  temperature  is  always 
subnormal  (97°) ;  the  pulse  small  and  weak.  The  tongue  is  distinctly  swollen ; 
the  speech  is  thick  ;  she  says  she  feels  as  if  she  could  not  get  the  words  out ;  she 
occasionally  has  some  difficulty  in  swallowing;  but  the  throat  does  not  appear 
to  be  swollen.  Her  mental  condition  is  quite  active  and  bright ;  throughout 
the  whole  course  of  her  illness  there  has  never  been  the  least  sign  of  mental 
impairment ;  sleep  natural.  She  is  very  feeble,  and  slow  in  her  movements. 
For  the  past  seven  years  she  has  been  quite  unable  to  attend  to  her  household 
duties,  and  has  had  to  have  a  housekeeper  and  companion.  The  urine  is  free 
from  albumen;  the  appetite  is  poor;  she  occasionally  suffers  from  diarrhoea. 
The  heart's  action  is  very  feeble,  but  the  organs  appear  to  be  healthy.  No 
thyroid  gland  can  be  felt. 

Noteworthy  and  exceptional  symptoms. — Mental  condition  quite  active  and 
bright ;  throughout  the  whole  course  of  her  illness  there  had  never  been  the 
least  sign  of  mental  impairment;  occasional  diarrhoea. 

Thyroid  treatment  commenced  23rd  January  1893. 

Preparation  a?id  Dose. — At  first  raw  gland  (|th  daily);  afterwards  dried 
extract  (gr.  v.  every  second  or  third  day). 

Immediate  results  of  treatment. — Rapid  improvement  and  complete  dis- 
appearance of  all  the  myxcedematous  symptoms. 

Subsequent  progress. — At  the  end  of  six  months,  she  felt  so  well  and  active 
that  she  was  able  to  dismiss  the  housekeeper  and  companion  whom  she  had 
had  for  seven  years,  and  to  undertake  all  her  household  duties  herself.  She 
looked  many  years  younger  than  she  did  before  the  treatment  commenced. 

Continues  to  take  gr.  v.  thyroid  extract  every  third  day. 

On  27th  May  1898  her  medical  attendant  wrote  me: — "The  patient  is  quite 
well  both  in  body  and  mind,  able  to  do  all  her  household  duties  herself;  takes 
her  food  well;  her  hair  has  grown  in  thick  and  of  the  natural  shade,  not  grey. 
She  takes  one  tabloid  every  second  night." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  160. 

CASE.  XIII. —  Typical  Myxcedema;  Rapid  Disappearance  of  All  the  Symptoms 
under  Thyroid  Treatment. 

Female,  aged  50,  widow,  fifteen  children,  seen  in  consultation  26th  January 
1893,  suffering  from  typical  myxcedema. 

Duration.  —  3  years. 

Apparent  cause. — None  ;  ?  cessation  of  menses. 

Present  condition. — All  the  characteristic  symptoms  of  myxcedema  are  pre- 
sent.    The  patient  complains  of  debility,  and  is  somewhat  anaemic.     The  body 


MYXCEDEMA.  35 1 

is  bulky;  the  face  is  broad  and  swollen,  the  lips  thick,  the  eyelids  puffy,  the 
skin  of  the  face  of  a  dingy  yellow  colour ;  a  pink  blush  is  present  on  each  cheek. 
The  hair  is  scanty  and  dry.  The  hands  are  spade-like  ;  the  feet  large  and 
swollen.  The  tongue  and  buccal  mucous  membrane  are  swollen ;  the  speech 
thick  and  slow ;  the  tongue  feels  too  big  for  the  mouth ;  the  patient  often  ex- 
periences a  choking  sensation  when  she  swallows.  Elastic  swellings  are  present 
above  the  clavicles.  Her  eyes  and  nose  often  run,  but  there  is  no  increased 
secretion  of  saliva.  The  skin  is  harsh  and  dry;  she  never  sweats;  the  tempera- 
ture is  subnormal  ;  she  feels  the  cold  intensely.  Her  memory,  sight,  and 
hearing  are  distinctly  impaired  ;  she  frequently  suffers  from  headache.  The 
feet  swell  at  night.  The  heart's  action  and  sounds  are  feeble,  pulse  65.  The 
appetite  poor  ;  bowels  constipated.  The  urine  does  not  contain  any  albumen. 
The  thyroid  gland  cannot  be  felt. 

Thyroid  treatment  commenced  27th  January  1893. 

Preparation  and  Dose. — At  first  the  raw  gland  (|th)  twice  a  week  ;  then  5 
grs.  of  dried  extract  every  other  day. 

Immediate  results  of  treatment. — In  the  course  of  six  weeks  the  myxcede- 
matous  symptoms  had  almost  entirely  disappeared  and  the  hair  was  growing. 
In  the  course  of  six  months,  the  patient  was  quite  well. 

Subsequent  progress. — The  patient  has  continued  quite  well.  On  3rd 
December  1896  she  looked  many  years  younger  than  she  previously  did.  Is 
taking  one  gr.  v.  tabloid  about  once  a  week. 

On  1 5th  April  1896  her  medical  attendant  wrote  me  saying  that  she  was  quite 
well,  and  that  she  still  continues  to  take  5  grs.  of  the  dried  extract  every  other  day. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  161. 

CASE  XIV. —  Very  Advanced  Myxoedema  of  Thirty-Four  Years'  Duration  in  a 
Patient  aged  73 ;  Decided  Improvement  lender  Ihyioid  Treatment ; 
Death  Two  Months  after  Discharge  from  Hospital. 

Female,  aged  73,  widow,  seven  children,  was  admitted  to  the  Edinburgh 
Royal  Infirmary  on  3rd  June  1893,  suffering  from  typical  and  advanced  myxoe- 
dema ;  for  fifteen  years  almost  entirely  confined  to  bed. 

Duration. — 34  years. 

Apparent  cause. — None. 

Condition  on  admission. — The  case  is  highly  characteristic  of  myxoedema  in 
its  advanced  (atrophic)  stage.  The  swelling,  though  still  considerable,  is  much 
less  marked  than  it  was  fifteen  years  ago  ;  the  body  is  very  bulky  ;  the  hands 
and  feet  swollen ;  the  upper  eyelids  are  more  swollen  than  in  any  other  case  of 
myxoedema  which  I  have  seen.  The  patient  is  extremely  weak  ;  her  move- 
ment, speech,  and  intellectual  processes  are  very  slow  and  deliberate ;  the  memory 
is  bad.  The  face  is  markedly  swollen  ;  the  upper  eyelids  completely  cover  the 
balls  ;  when  the  patient  is  asked  to  look  at  an  object,  she  raises  the  swollen 
lid  with  the  finger,  so  as  to  expose  the  pupil.  The  lips  are  large,  tense,  and 
elastic,  the  lower  lip  markedly  pendulous.  The  skin  of  the  face  has  a  dingy 
yellow  tint ;  a  pink  blush  is  present  on  each  cheek.  Supraclavicular  swellings 
are  present.  The  scalp  is  almost  entirely  bald,  but  is  not  covered  with  crusts 
or  scabs.  The  eyebrows  and  eyelashes  are  entirely  wanting.  The  skin  is  very 
harsh,  rough,  and  dry.  The  patient  feels  the  cold  intensely,  and  never  sweats. 
She  complains  that  her  feet  and  hands  are  always  cold,  and  that  she  frequently 
feels  as  if  cold  water  were  being  poured  down  her  back.  Many  flat  and  stalked 
warts  are  present  on  different  parts  of  the  body.     They  have  for  the  most  part 


352  DISEASES   OF   THE    BLOOD   GLANDS. 

developed  since  the  disease  commenced.  A  large  smooth  wart-like  projection, 
the  size  of  a  small  cherry,  protrudes  from  the  gum  of  the  lower  jaw,  between 
the  incisor  teeth.  The  tongue  is  large  and  swollen  ;  a  fiat  button-like  wart 
projects  from  the  dorsum,  close  to  the  tip.  The  speech  is  very  characteristic, 
thick,  slow,  and  monotonous,  the  voice  harsh  and  rough ;  the  patient  says  she 
feels  as  if  the  words  stuck  in  her  mouth.  She  has  considerable  difficulty  in 
swallowing  ;  the  throat  is  swollen  ;  saliva  flows  from  the  mouth  at  night. 
Memory,  sight,  and  hearing  are  impaired.  The  temperature  is  subnormal 
(average  970)  ;  the  pulse  slow  (64) ;  the  respirations  normal  (22).  There  is  some 
ordinary  oedema  of  the  feet.  The  urine  contains  a  slight  trace  of  serum  albumen, 
no  globulin,  and  no  casts.  The  appetite  is  poor.  She  sleeps  very  badly,  and  is 
often  disturbed  by  unpleasant  dreams.     The  thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — In  order  to  see,  the  patient  has  to 
raise  the  greatly  swollen  eyelid  with  the  finger  ;  a  large  smooth  wart-like  pro- 
jection the  size  of  a  small  cherry  protrudes  from  the  gum  of  the  lower  jaw, 
between  the  incisor  teeth  ;  a  flat  button-like  wart  is  present  on  the  dorsum  of 
the  tongue  near  the  tip. 

Thyroid  treatment  commenced  on  5th  June  1893. 

Preparation  and  Dose. — B.  &  M.'s  liquid  extract,  5-7  minims  daily.  Strych- 
nine and  strophanthus.  The  thyroid  was  not  well  borne  and  had  to  be  given 
intermittently. 

Immediate  results  of  the  treatment. — Faintness,  sickness,  headache,  epigas- 
tric pain,  diarrhoea,  rise  in  temperature  and  pulse,  difficulty  in  breathing,  marked 
diminution  of  the  myxoedematous  symptoms,  growth  of  hair,  some  desquama- 
tion of  skin.     Fainting  attack  when  up  at  stool  during  the  course  of  treatment. 

Date  of  discharge. — Patient  insisted  on  leaving  the  hospital  on  31st  August 
1893. 

Subsequent  progress  of  case.  The  myxoedematous  symptoms  lessened,  the 
hair  continued  to  grow,  the  diarrhoea  continued,  patient  refused  to  continue  the 
thyroid.  She  died  suddenly,  apparently  from  cardiac  syncope,  on  26th  November 
1893.     Had  not  taken  any  thyroid  for  more  than  2  months  before  death. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  143. 

CASE  XV. —  Typical  Myxcedema  ;  Rapid  Disappeara?ice  of  All  the  Symptoms 
under  Thyroid  Treatment. 

Female,  aged  51,  married,  seven  children,  seen  24th  June  1893,  suffering 
from  typical  myxcedema.  She  brought  her  daughter  to  consult  me,  and  was 
surprised  when  I  told  her  she  herself  was  suffering  from  a  definite  disease 
(myxcedema) ;  she  thought  her  condition  was  due  to  "fat  and  debility." 

Duration. — 20  years. 

Apparent  cause.     None. 

Present  condition. —  The  patient  complained  of  debility,  and  was  some- 
what anaemic.  Supraclavicular  swellings  large.  The  body  was  very  bulky  ;  the 
face,  hands,  feet,  and  abdomen  swollen.  Her  eyelids  were  swollen  ;  the  skin 
of  the  face  dingy  yellow  in  colour  ;  a  pink  blush  was  present  on  each  cheek;  the 
lips  were  thick,  elastic,  and  of  a  bluish  colour;  the  tongue  large;  the  throat 
swollen.  The  hair  was  scanty;  the  scalp  not  encrusted;  the  skin  dry.  The 
patient  stated  that  she  felt  the  cold  intensely,  and  never  sweated.  The  tem- 
perature was  subnormal.  The  speech  was  thick  and  characteristic.  The 
memory  was  bad.  The  feet  and  legs  were  cedematous.  The  appetite  poor  ; 
the  bowels  constipated.     The  urine  was  free  from  albumen.     The  pulse  was 


MYXCEDEMA.  353 

small  and  weak  ;  the  heart  sounds  very  feeble,  and  the  cardiac  impulse  imper- 
ceptible, probably  the  result,  in  part  at  least,  of  the  thickness  of  the  chest  walls; 
the  pulse  slow  (58).     The  thyroid  gland  could  not  be  felt. 

Noteworthy  and  Exceptional  Symptoms. — An  extremely  stout  woman. 

Thyroid  treatment  commenced  30th  June  1893. 

Preparatiorz  and  Dose. — Liquid  extract  (D.  &  F.'s)  51  ter  die  (=  £th  gland). 

Immediate  results  of  treatment. — Rapid  disappearance  of  myxedematous 
symptoms  ;  lost  1  st.  5  lbs.  during  the  treatment.  Says  she  looks  and  feels  a 
different  person,  so  active  and  energetic. 

Subsequent  progress. —  On  lgth  April  1898,  she  wrote  me  saying  that  she 
was  keeping  well  though  short  of  breath ;  she  had  had  one  attack  of  dyspnoea 
(apparently  cardiac)  through  the  night ;  she  had  discontinued  the  tabloids  for 
about  4  months,  but  had  to  begin  them  again  as  she  felt  she  was  getting  stouter  ; 
she  now  takes  two  5  grain  tabloids  twice  or  thrice  a  week;  her  present  weight 
is  \t>\  st. 

Recorded  in  full  in  the  "  Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  172. 

CASE  XVI. —  Typical  Myxedema  of  Two  Years'  Duration  ;  Rapid  Disappear- 
ance of  All  the  Myxoedematous  Symptoms  under  Thyroid  Treatment. 

Female,  aged  60,  married,  five  children,  seen  in  consultation  on  25th  July 
1893,  suffering  from  typical  myxcedema. 

Duration. — About  2  years. 

Apparent  cause. — None. 

Present  condition. — The  appearance  is  highly  characteristic.  The  body  is 
bulky,  the  face  moon-shaped,  the  hands  spade-like,  the  feet  broad,  the  abdomen 
large  and  pendulous,  the  eyelids  markedly  swollen  (bags  of  fluid),  the  lips  thick 
and  elastic,  and  of  a  bluish  tint,  the  hair  scanty,  the  scalp  covered  with  dirty 
brown  crusts.  A  pink  blush  is  present  on  each  cheek.  The  tongue  is  very 
large,  and  the  buccal  mucous  membrane  swollen  ;  the  speech  is  very  thick,  the 
memory  impaired,  the  cerebration  slow  ;  she  sleeps  well.  The  skin  is  harsh 
and  dry,  and  of  a  dingy  yellow  colour.  The  patient  states  that  she  feels  the 
cold  intensely,  and  that  she  never  sweats.  She  feels  very  debilitated,  and 
unequal  to  any  exertion.  Large  elastic  swellings  are  present  above  the  clavicles. 
The  temperature  is  subnormal  (97°  to  97°.8).  The  feet  swell  at  night.  The 
appetite  is  poor  ;  the  bowels  regular.  The  urine  is  free  from  albumen.  The 
radial  pulse  is  76,  and  of  good  strength.  The  aortic  second  sound  is  markedly 
accentuated.     The  thyroid  gland  cannot  be  felt. 

Thyroid  treatment  commenced  26th  July  1898. 

Preparatiott  and  Dose. — Raw  gland  (|th)  every  other  day. 

Immediate  results  of  treatment. — Rapid  improvement ;  in  the  course  of  three 
months  the  myxoedematous  symptoms  had  completely  disappeared. 

Subsequent  progress. — The  patient  has  continued  in  excellent  health. 

On  10th  April  1898  she  wrote  me  : — ■"  I  have  much  pleasure  in  stating  that 
my  health  has  been  pretty  good  for  some  time  back  ;  but  I  find  that  the 
thyroid  has  to  be  taken  regularly  once  a  week,  otherwise  the  old  symptoms 
become  noticeable.  I  have  been  in  the  habit  of  taking  either  the  half  of  a  small 
or  the  third  of  a  large  one  (lobe).  For  several  weeks,  however,  I  have  felt  the 
necessity  of  taking  that  quantity  twice  in  the  week.  I  have  not  been  so  much 
troubled  with  sickness  as  formerly,  and  though  not  feeling  very  strong  (patient 
is  65  years  of  age)  my  health  has  been  pretty  fair." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  163. 

Z 


354  DISEASES   OF   THE   BLOOD   GLANDS. 

CASE  XVII.  —  Typical  Jlyxa'dema,  following  Exophthalmic  Goitre;  Dis- 
appearance of  the  Myxedematous  Symptoms  tender  Thyroid  Treatment. 

Female,  aged  55,  single,  seen  in  consultation  5th  August  1893,  suffering 
from  typical  myxoedema. 

Duration. — 2  years  ;  had  previously  suffered  for  6  years  from  typical  ex- 
ophthalmic goitre  and  heart. 

Apparent  cause. — Atrophy  of  the  thyroid  gland  following  exophthalmic 
goitre. 

Present  condition. — The  patient  complains  of  debility  and  loss  of  mental 
vigour ;  she  is  distinctly  anaemic.  The  eyelids  are  markedly  swollen,  bags  of 
fluid  are  present  below  the  eyes ;  the  lips  are  full  and  thick  ;  the  skin  of  the 
face  is  of  a  yellow  tinge  ;  a  pink  blush  is  present  on  each  cheek  ;  the  eyebrows 
are  scanty  and  elevated  ;  the  hair  of  the  head  is  thinner  than  it  used  to  be. 
Elastic  swellings  are  present  above  the  clavicles.  The  thyroid  gland  cannot  be 
felt.  The  patient  states  that  she  usually  feels  chilly,  and  is  more  susceptible  to 
cold  than  she  used  to  be ;  but  that  several  times  in  the  course  of  the  day  a 
feeling  of  heat  and  flushing  passes  over  her.  She  states  that  she  is  very  easily 
tired,  and  unfit  for  any  exertion.  Her  memory  is  bad  ;  she  sleeps  well ; 
frequent  headache.  The  tongue  is  enlarged ;  the  speech  highly  characteristic — 
thick  and  slow.  The  skin  is  harsh  and  dry.  She  does  not  sweat.  The  hands 
are  swollen  ;  she  is  obliged  to  wear  larger  gloves  than  she  did  a  year  ago. 
The  feet  are  broad,  and  there  is  some  ordinary  oedema  of  the  ankles.  The 
abdomen  and  body  generally  are  much  swollen.  The  temperature  is  sub- 
normal. The  menstruation  ceased  ten  years  ago.  The  urine  is  free  from 
albumen.  The  heart's  action  is  natural,  except  that  the  first  sound  appears  to 
be  reduplicated ;  the  pulse  70  ;  still  occasionally  has  palpitation.  The  appetite 
is  poor  ;  the  bowels  constipated. 

Noteworthy  and  exceptional  symptoms. — The  thyroid  gland  cannot  be  felt  ; 
several  times  a  day  a  feeling  of  heat  and  flushing  passes  over  her,  though  she 
usually  feels  chilly  and  is  more  susceptible  to  cold  than  she  used  to  be. 

Thyroid  treatment  commenced  6th  August  1893. 

Preparation  and  Dose. — Dried  extract,  gr.  v.  daily. 

Immediate  results  of  treatment. — Rapid  disappearance  of  the  myxcedematous 
symptoms  ;  desquamation  of  the  skin  and  growth  of  hair. 

Subsequent  progress.— Jth  May  1895. — Continues  perfectly  well;  the  only 
thing  she  complains  of  is  the  unpleasant  feeling  of  heat  and  flushing  which 
passes  over  the  body  sometimes  twenty  times  a  day. 

gth  April  1898. — Though  60  years  of  age  does  not  look  more  than  45.  For 
the  past  year  has  been  dyspeptic  and  troubled  with  her  heart,  but  otherwise 
quite  well.  The  flushings  continue.  She  continues  to  take  one  tabloid  (gr.  v. 
of  dried  extract)  every  other  day. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  170. 

CASE  XVIII. — Imperfectly  Developed  Myxedema ;  Rapid  Improvement  under 
Thy7~oid  Treatment. 

Female,  aged  67,  married,  six  children,  consulted  me  on  nth  October  1893, 
suffering  from  slight  myxoedema. 

Duration. — Probably  3  or  4  years  ;  worse  for  6  months. 

Apparent  cause. — None. 

Present  condition. — The  patient  complained  of  giddiness,  an  uneasy  feeling 
in  the  head,  lassitude,  debility,  loss  of  appetite,  uneasiness  in  the  region  of  the 


MYXCEDEMA.  355 

stomach,  and  dimness  of  vision.  The  face  was  pale,  the  eyelids  were  distinctly 
puffy  and  swollen  ;  the  urine  was,  and  always  had  been,  free  from  albumen ;  the 
skin  was  harsh  and  dry ;  the  patient  had  become  very  susceptible  to  cold,  and  did 
not  perspire  as  she  used  to  do.  The  hair  of  the  head  and  eyebrows  had  got 
markedly  thinner.  Physical  examination  failed  to  reveal  evidence  of  disease 
in  any  of  the  viscera. 

Thyroid  treatment  commenced  12th  October  1893. 

Preparation  and  Dose. — Liquid  extract  (D.  &  F.'s)  5ss.  ter  die  (=  ts  of  a 
gland)  ;  subsequently  dried  extract  (gr.  v.)  daily. 

Immediate  results  of  treatment. — Marked  and  rapid  improvement. 

Subsequent  progress.—  On  Sth  April  1898  her  doctor  wrote  me — "Patient 
continues  in  fairly  good  health  ;  she  goes  out  walking  most  days,  and  is  bright 
and  cheerful.  I  have  just  been  attending  her  for  a  fairly  smart  attack  of 
influenza  from  which  she  has  made  a  good  recovery.  Continues  to  take  one 
thyroid  tabloid  (5  grs.)  every  day  ;  if  she  ceases  taking  them  she  misses  them." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  174. 

CASE  XIX. — Typical  Myxcedema  :  Rapid  Disappearance  of  All  the  Symptoms 
tender  Thyroid  Feeding. 

Female,  aged  40,  widow,  six  children,  seen  in  consultation  on  9th  January 
1894,  suffering  from  typical  myxcedema. 

Duration. — 3  or  4  years. 

Apparent  cause. — None. 

Present  condition. — She  complains  of  a  feeling  of  great  languor  and  depres- 
sion, weakness  and  inability  to  exert  herself.  She  says  that  she  feels  scarcely 
able  to  walk  across  the  floor,  she  is  getting  so  heavy  and  weak.  There  is  some 
anaemia.  The  body,  abdomen,  face,  hands,  and  feet  are  much  larger  than  they 
used  to  be  ;  supraclavicular  swellings  well  marked  ;  tongue  large ;  throat 
swollen.  The  eyelids  and  lips  are  swollen.  The  skin  of  the  face  is  yellow  in 
colour  ;  a  slight  pink  blush  is  present  on  each  cheek.  The  hair  is  thin  and 
scanty,  and  much  darker  than  it  used  to  be  ;  skin  also  darker.  The  skin  is  very 
rough  ;  she  no  longer  perspires  as  she  used  to  do.  She  feels  the  cold  very  much ; 
her  temperature  is  subnormal.  Appetite  poor;  bowels  very  much  constipated. 
Her  memory  is  much  impaired  ;  she  sleeps  well.  The  voice  is  much  rougher 
and  harsher  than  it  used  to  be ;  the  articulation  is  slow  and  thick.  Menorrhagia ; 
•urine  normal.     Thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — Skin  and  hair  became  markedly 
darker  as  disease  advanced. 

Thyroid  treatment  commenced  10th  January  1894. 

Preparation  and  Dose. — Dried  extract ;  at  first  gr.  x.  daily  ;  after  five  days, 
reduced  to  gr.  v.  every  other  day.  The  larger  dose  produced  severe  aching  pains 
in  the  head,  back,  and  limbs  and  in  the  position  of  the  thyroid. 

Immediate  results  of  treatment.  —  Rapid  disappearance  of  all  the  myxe- 
dematous symptoms  and  complete  restoration  of  health. 

Subsequent  progress. — On  iind  May  1895,  when  I  next  saw  the  patient,  I 
did  not  know  her.  She  says  she  feels  perfectly  well.  She  states  that  her  skin  is 
much  darker  than  it  used  to  be  (Dr  Lundie  confirms  this),  and  that  her  hair  is  so 
much  darker  that  her  sister  said  to  one  of  the  children,  "What !  is  your  mother 
dyeing  her  hair?"  Her  hair  is  now  quite  black;  it  used  to  be  dark  brown  in 
colour.  She  showed  me  a  specimen  of  the  hair  cut  off  twelve  years  ago  ;  it  was 
then  nut-brown  in  colour.     The  contrast  between  the  present  black  and  the 


356  DISEASES   OF   THE   BLOOD   GLANDS. 

former  brown  is  very  striking.  Since  she  commenced  to  take  the  thyroid,  her 
hair  has  got  much  thicker;  it  is  also  much  softer  than  it  used  to  be.  The  nipples 
are  not  any  darker  than  they  used  to  be. 

She  states  that  during  the  past  eighteen  months  she  has  twice  omitted  to  take 
the  tabloids  for  some  weeks  at  a  time,  but  has  always  been  obliged  to  return  to 
them  again.  After  omitting  the  remedy  for  a  month,  she  on  both  occasions 
began  to  suffer  from  the  old  symptoms.  She  felt  on  each  occasion  as  if  there 
was  something  at  the  bottom  of  the  throat  (placing  her  hand  over  the  region  of 
the  thyroid)  which  ought  to  come  away.  For  the  last  four  months  she  has  taken 
one  thyroid  tabloid  every  other  day. 

12th  April  1898. — Called  to  see  me  to-day.  Looks  quite  well.  Says  she  has 
been  perfectly  well  ever  since  the  last  note  ;  able  to  do  hard  work  both  of  body 
and  mind  ;  her  skin  is  quite  smooth,  but  the  skin  and  hair  continue  to  get  darker  ; 
she  still  feels  the  cold  a  good  deal  ;  menstruation  regular,  but  much  more  pro- 
fuse than  it  used  to  be.  About  a  year  ago  left  off  the  thyroid  for  a  month,  and  felt 
the  same  pain  and  choking  feeling  in  the  throat  that  she  used  to  have;  it  passed 
off  as  soon  as  she  again  resumed  the  medicine.    Is  taking  2  or  3  tabloids  a  week. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  185. 

CASE  XX. —  Typical  Myxedema  ;  Temporary  Paralysis  of  the  Right  External 
Rectus  Muscle ;  Rapid  Improveme7it,  and  Disappearance  of  the  Myxe- 
dematous Symptoms  under  Thyroid  Treatment. 

Female,  aged  60,  married,  two  children,  seen  in  consultation  4th  April  1894,. 
suffering  from  typical  myxcedema. 

Duration. — 2  years  at  least. 

Apparent  cause. — None. 

Present  condition.  —  The  right  external  rectus  was  partly  paralysed  ;  the 
double  vision  developed  suddenly,  and  without  obvious  cause. 

The  case  presented  all  the  characteristic  symptoms  of  myxcedema.  The 
patient  complained  of  great  debility.  The  body  was  bulky ;  the  abdomen,  hands, 
and  feet  were  enlarged.  There  was  some  ana?mia.  The  face  was  swollen,  the 
skin  of  a  dingy  yellow  hue,  the  eyelids  puffy,  the  lips  were  thick  and  firm,  the 
tongue  large,  the  speech  deliberate  and  thick.  There  was  no  pink  blush  on  the 
cheeks.  The  tongue  was  large.  Elastic  swellings  were  present  above  the  clavicles. 
The  eyebrows  were  very  scanty,  and  the  hair  of  the  head  thin,  it  had  been  coming- 
out  for  the  past  two  years  ;  the  scalp  was  covered  with  dirty  brown  crusts,  the  skin 
generally  harsh  and  dry.  The  patient  stated  that  she  felt  the  cold  much  more 
than  she  used  to  do  a  few  years  ago,  and  that  she  never  sweated.  The  tempera- 
ture was  subnormal  (97.4°  F.) ;  the  radial  pulse  80,  and  of  good  strength  ;  the 
aortic  second  sound  accentuated.  Her  memory  was  impaired,  and  her  cerebra- 
tion slow ;  sight  and  hearing  impaired  ;  sleep  natural.  The  urine  was  free  from 
albumen.  The  optic  discs  were  natural.  The  appetite  was  poor  ;  bowels  con- 
stipated. There  was  no  evidence  of  any  intracranial  or  other  visceral  disease. 
The  thyroid  gland  could  not  be  felt. 

Noteworthy  and  exceptional  symptoms. — Temporary  paralysis  of  the  right 
external  rectus  muscle. 

Thyroid  treatment  commenced  5th  April  1894. 

Preparation  and  Dose. — Dried  extract  ;  at  first  gr.  v.  afterwards  gr.  x.,  daily. 

Immediate  results  of  treatment.  —  In  the  course  of  a  fortnight  the  dyspepsia 
and  paralysis  of  the  external  rectus  disappeared  and  all  the  myxedematous 
symptoms  rapidly  disappeared. 


MYXCEDEMA.  357 

Subsequent  progress. — ind January  1898. — Patient  seen  to-day  and  looks  a 
very  young  woman  for  her  age.  She  tells  me  that  she  has  been  perfectly  well 
since  the  treatment  was  commenced.  She  says  the  result  has  been  wonderful. 
She  was  blind  and  deaf  and  had  lost  her  hair  ;  these  symptoms  have  all  disap- 
peared. She  has  taken  the  thyroid  from  time  to  time,  but  not  regularly.  Advised 
to  take  half  a  tabloid  (gr.  i\  of  dried  extract)  every  day. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  175. 


CASE  XXI. —  Typical  Myxcedema  ;  Rapid  Disappearance  of  All  the  Symptoms 
under  Thyroid  Treatment. 

Female,  aged  31,  married,  five  children,  seen  in  consultation  9th  May  1894, 
suffering  from  typical  myxcedema. 

Duration. — 3  years. 

Apparent  cause.—  None. 

Present  condition. — The  patient  complains  of  weakness,  and  says  that  she  is 
unfit  for  any  exertion.  She  feels  the  cold  very  much  more  than  she  used  to  do, 
and  is  always  worse  in  winter.  She  is  distinctly  anaemic.  The  face,  hands,  feet, 
abdomen,  and  body  generally  are  swollen.  The  lower  lids  are  puffy;  the  lips 
large,  swollen,  and  thick ;  the  skin  of  the  face  of  a  dingy  yellow  colour ;  a  pink 
blush  is  present  on  each  cheek.  Supraclavicular  swellings  present.  The  hair 
of  the  head  is  very  dry  and  harsh  ;  the  scalp  dry  and  dirty  ;  the  skin  is  remark- 
ably harsh  and  dry;  on  the  face,  hands,  knees,  and  legs  it  is  so  rough,  that  when 
the  finger  is  passed  over  it  it  feels  like  a  file.  The  patient  states  that  for  some 
time  past  she  has  never  sweated,  and  that  she  always  feels  cold.  The  speech  is 
thick,  the  tongue  large ;  she  often  has  a  choking  feeling,  as  if  the  tongue  were 
too  large  for  the  mouth  ;  the  throat  swollen.  At  night  the  saliva  often  flows  out 
of  the  mouth,  "  because,"  she  says,  "  it  does  not  go  down."  The  memory  is  not 
impaired;  she  sleeps  well.  The  appetite  is  poor  ;  the  bowels  constipated.  The 
temperature  is  subnormal  (980  F.)  ;  the  pulse  70,  and  weak.  The  urine  is  free 
from  albumen  ;  the  menstruation  regular.     The  thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — Increased  flow  of  saliva  from  the 
mouth  at  night. 

Thyroid  treatment  commenced  9th  May  1894. 

Preparation  a?id  Dose.— Dried  extract  gr.  v.  daily,  increased  to  gr.  x.  for  a 
time. 

Immediate  effects  of  treatment. — Rapid  disappearance  of  all  of  the  myxce- 
■dematous  symptoms  and  restoration  of  health  and  strength. 

Subsequent  progress. — On  2nd  January  1898,  her  doctor  wrote  me  : — "The 
patient  has  continued  quite  well  ;  she  had  a  child  lately  and  lost  much  blood 
after  delivery ;  this  has  pulled  her  down  a  good  deal,  but  she  has  picked  up  again 
since.  She  continues  to  take  one  tabloid  (gr.  v.  thyroid  extract)  every  other 
day." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  176. 


CASE  XXII.  —  Typical  Myxcedema ;  Rapid  Disappearance  of  all  the  Myxe- 
dematous Symptoms  under  Thyroid  Treatment. 
Female,  aged  60,  widow,  nine  children,  was  seen  as  an  out-patient  at  the 
Edinburgh  Royal  Infirmary  on  7th  July  1894,  suffering  from  typical  myxcedema. 
Her  appearance  was  so  characteristic  that  while  she  was  standing  at  the  end  of 


358  DISEASES   OF   THE   BLOOD   GLANDS. 

a  long  passage  (away  from  me  at  a  distance  of  60  feet)  I  said  to  my  assistant 
Dr  Douglas,  ''That  old  lady  looks  as  if  she  had  myxcedema." 

Duration. — 3  years. 

Apparent  cause. — None. 

Condition  on  admission. — The  patient  complains  of  great  debility.  The  body 
is  very  bulky;  abdomen,  hands,  and  feet  enlarged.  The  face  is  broad,  swollen, 
and  of  a  dingy  yellow  colour  ;  the  lips  are  thick,  elastic,  and  tense  ;  the  eyelids 
are  so  markedly  swollen  that  all  of  the  students  who  saw  the  patient  came  to  the 
conclusion  that  she  was  suffering  from  Bright's  disease ;  a  pink  flush  is  present 
on  each  cheek.  The  buccal  mucous  membrane  is  anaemic.  Large  elastic 
swellings  are  present  above  each  clavicle.  The  hair  is  scanty;  the  scalp  covered 
with  dirty  brown  crusts  ;  the  skin  is  very  dry  and  harsh ;  the  patient  states  that 
she  never  sweats  ;  she  says  that  she  always  feels  cold,  and  that  when  the  room 
is  so  hot  that  other  people  complain  of  the  heat,  she  only  feels  comfortable.  The 
temperature  is  subnormal.  The  speech  is  thick,  and  highly  characteristic.  The 
tongue  is  large  and  the  throat  swollen  ;  the  patient  complains  of  difficulty  of 
swallowing.  The  memory,  sight,  and  hearing  are  considerably  impaired.  The 
appetite  is  poor  ;  the  bowels  constipated.  The  urine  contains  a  considerable 
quantity  of  albumen,  but  no  casts  ;  its  specific  gravity  is  1008.  The  thyroid 
gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — The  urine  contained  a  considerable 
quantity  of  albumen  but  no  casts. 

Thyroid  treatment  commenced  8th  July  1894. 

Preparation  and  Dose. — Five  grains  of  dried  extract  daily. 

Immediate  results  of  treatment. — Complete  disappearance  of  all  the  myxce- 
dematous  symptoms,  free  desquamation  of  skin,  growth  of  hair,  etc. 

Subsequent  progress.  —  \oth  May  1895. — Looks  10  years  younger;  all  the 
myxedematous  symptoms  have  disappeared.  Stated: — "  Every  one  that  sees 
me  could  not  believe  it  was  me,  such  a  change."  Can  now  do  her  housework  ; 
was  not  able  to  do  this  for  10  years  previously.  Advised  to  continue  gr.  v.  of  the 
dried  extract  every  other  day;  also  arsenic  and  iron  as  is  anaemic. 

gth  April  1898. — Seen  to-day.  Says  she  has  been  keeping  very  well  since 
last  seen  until  3  weeks  ago  ;  she  then  left  off  the  tabloids  and  has  not  taken 
them  since.  Has  felt  a  return  of  the  old  symptoms — languor,  numbness  in  legs, 
swelling  of  abdomen  and  face.  Has  on  several  previous  occasions  left  off  the 
tabloids  for  a  week,  but  always  had  to  resume  them  again  because  she  did  not 
feel  so  well.  One  tabloid  (gr.  v.)  every  night  keeps  her  in  good  health.  Lower 
lip  to-day  rather  swollen  ;  head  still  scaly;  otherwise  seems  all  right.  Advised 
to  resume  the  thyroid  at  once  and  take  it  regularly. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  150. 


CASE  XXIII.—  Commencing  Myxcedema,  Complicated  with  Diarrka'a ;  Rapid 
Improvement  under  Thyroid  Treatment. 

Male,  aged  66,  married,  seen  in  consultation  on  8th  August  1S94,  suffering 
from  myxcedema. 

Duration. — Several  (probably  7)  years. 

Apparent  cause.  — Mental  shock. 

Present  condition. — The  patient  complains  of  debility,  and  inability  to  undergo 
either  physical  or  mental  exertion.  His  face  is  pale  and  sallow  looking,  the  lower 
eyelids  markedly  swollen,  the  lips  thick,  swollen,  and  slightly  blue;  his  hair  has 


MYXCEDEMA.  359 

been  getting  thinner  lately;  his  speech  is  distinctly  slow  and  thick,  but  he  has 
not  himself  noticed  that  it  is  different  to  what  it  used  to  be  when  he  was  well. 
His  hands  and  feet  are  larger  than  they  used  to  be.  The  skin  is  thick  and  coarse, 
but  he  says  that  he  perspires  easily  on  exertion.  He  complains  that  he  feels  the 
cold  much  more  than  he  used  to  do;  he  says  that  he  never  feels  warm  even  in 
summer.  The  temperature  is  normal.  His  eyes  and  nose  frequently  run.  His 
memory  and  hearing  are  impaired ;  sleeps  excessively.  The  tongue  is  large,  the 
throat  somewhat  cedematous,  the  appetite  poor,  the  bowels  frequently  loose. 
The  urine  is  free  from  albumen;  it  contains  a  slight  trace  of  sugar.  No  thyroid 
gland  can  be  felt. 

The  case  was  not  typical,  but  some  of  the  symptoms,  notably  the  swelling  of 
the  face,  hands,  and  body  generally,  the  increased  thickness  and  roughness  of 
the  skin,  the  increased  sensibility  to  cold,  and  loss  of  hair,  were  highly  suggestive 
of  commencing  myxcedema. 

Noteworthy  and  exceptional  symptoms.  —  Occasional  attacks  of  severe 
diarrhoea;  perspires  on  exertion  ;  urine  contains  a  trace  of  sugar. 

Thyroid  treatment  commenced  on  9th  August  1894.  Also  salicylate  of 
bismuth  for  diarrhoea. 

Preparation  and  Dose. — Dried  extract,  gr.  v.  daily. 

Immediate  results  of  treatment. — Rapid  improvement.  On  20th  August  was 
better  than  he  had  been  for  6  months  previously. 

Subsequent  progress. — On  \t\th  May  1895,  tne  patient  wrote  to  me  : — "  I 
saw  Dr  Miller  yesterday,  and  he  suggested  that  I  should  write  out  a  statement 
of  my  case,  which  I  do  so  much  the  more  willingly  that  I  consider  myself,  and 
those  whose  breadwinner  I  am,  under  very  great  obligation  to  you.  This  is  the 
state  I  was  in  just  about  a  year  ago  : — 

To  begin  at  the  top.  My  hair  was  getting  fluffy,  and  coming  out  rapidly. 
My  eyes  were  constantly  weeping,  and  my  nose  running.  I  had  great  bags  under 
my  eyes,  and  my  cheeks  were  puffy  and  hanging,  bobbing  up  and  down  as  I 
walked  along.  My  whole  body  was  enormously  swollen,  especially  my  hands, 
which  I  could  scarcely  shut,  and  my  legs  from  the  knee  downwards.  My  legs 
were  so  heavy  that  I  had  literally  to  drag  them  along.  Once  at  Birnam,  thinking 
I  was  going  to  miss  the  train,  I  tried  to  run ;  the  impetus  sent  my  body  forward, 
but  the  legs  would  not  go — result,  a  very  heavy  fall.  For  at  least  two  years,  but 
especially  during  the  last  year  of  my  illness,  I  suffered  very  much  from  cramp. 
If  I  did  not  lie  straight  in  bed,  if  I  put  up  my  feet  to  get  my  boots  laced  (I  had 
got  terribly  awkward  in  stooping),  or  going  downstairs,  my  legs  got  terribly 
cramped ;  you  could  quite  distinctly  see,  sticking  out  under  my  trousers,  in  the 
front  part  of  my  thighs,  lumps  as  big  as  a  large  egg.  These  cramps  have  now 
entirely  disappeared.  I  had  a  terrible  catarrh;  every  time  I  coughed  or  sneezed 
I  felt  intense  pain,  as  if  my  inside  were  being  torn  to  shreds.  The  action  of  the 
heart  was  very  unsatisfactory;  it  took  me  two  hours  one  day  to  walk,  panting 
and  puffing,  from  Broughty  Ferry  to  Monifieth — z\  miles — whereas  I  used  quite 
easily  to  walk  4  miles  an  hour.  Always,  after  about  ten  minutes'  walk,  my  left 
arm  got  perfectly  benumbed,  quite  dead.  My  hands  and  my  lips  were  constantly 
blue,  my  feet  always  intensely  cold,  the  heels  very  painfully  so,  as  if  they  were 
plunged  in  ice-water.  The  skin  on  my  heels  grew  to  an  abnormal  thickness  ;  I 
used  to  pare  it  with  a  big  iron  file.  I  was  frequently  obliged  to  make  water — 
had  always  to  get  up  twice  during  the  night.  A  heavy  torpid  sleep  two  hours 
and  a  half  after  dinner;  no  sooner  in  bed  than  I  was  asleep.  Sometimes  stayed 
in  bed  on  Sunday,  sleeping  the  whole  day,  and  all  the  time  a  tremendous  snore 


360  DISEASES   OF   THE   BLOOD   GLANDS. 

which  could  be  heard  all  over  the  house.  (Never  used  to  snore  before.)  Finally, 
a  terrible  diarrhoea,  which  began  about  the  middle  of  August  1894,  and  culmi- 
nated towards  June  in  five  or  six  stools  a  day,  perfectly  liquid,  the  smell  of  the 
evacution  being  most  offensive.    I  got  so  weak  that  I  frequently  staggered  across 

the  pavement  like  one  drunk.     The  Rev.  Mr told  me  a  few  days  ago  that 

one  day  he  said  to  his  astonished  family,  '  If  I  did  not  know  Mr  D.  to  be  a  sober 
man,  I  should  say  he  was  drunk  this  afternoon.'  He  had  seen  me  in  one  of  my 
staggers.  I  was  under  the  impression,  until  a  few  days  ago,  that  my  mind  had 
not  been  affected,  but  it  seems  I  was  wrong.  Dr  Miller  told  me  he  noticed  that 
I  was  getting  slow  in  taking  up  an  idea,  and  slow  in  expressing  myself.  I  was 
also  getting  deaf.  Dr  M'Bride,  whom  I  consulted  on  18th  October  1894,  told 
me  that  my  deafness  arose  from  the  myxcedema,  and  would  be  cured  by  the 
tabloids,  and  my  hearing  is  decidedly  better. 

I  commenced  your  treatment  on  the  10th  of  August.  By  the  end  of  the  month 
I  was,  I  may  say,  well.  The  swelling  of  my  body  was  fast  disappearing,  and  then 
the  terrible  drain  on  my  system  (diarrhoea)  began  to  show  itself;  there  was 
nothing  left  of  me  but  skin  and  bone.  My  strength  returned  rapidly.  All  the 
ugly  symptoms  mentioned  above  have  disappeared,  and  Saturday  three  weeks 
ago  I  played  two  rounds  on  the  Monifieth  links  with  a  young  and  strong  player, 
a  fast  walker,  and  improved  considerably  in  the  second  round.  I  still  continue 
the  tabloids,  one  every  other  night. 

I  fancy  my  illness  must  have  been  brewing  for  years.  So  far  as  I  can  recol- 
lect, the  bags  under  my  eyes,  which  have  now  quite  disappeared,  began  to  form 
about  seven  years  ago;  then  I  got  eczema,  and  finally  myxcedema." 

On  \oth  April  1898,  patient  again  wrote  : — "I  continue  taking  the  tabloids, 
generally  three  times  a  week,  one  at  a  time.  There  seems  to  be  no  trace  of 
myxcedema  about  me,  I  am  looking  remarkably  well  and  vigorous ;  the  only 
unfavourable  symptom  is  that  my  hands  are  frequently  blue.  You  may  recollect 
that  when  I  first  consulted  you  I  was  terribly  bloated ;  at  the  end  of  three  weeks 
under  your  treatment,  all  that  puffing  had  gone  down  and  I  weighed  exactly  ten 
stone,  which,  for  a  man  of  5  ft.  95  ins.,  broad-shouldered  and  deep-chested,  is 
uncommonly  little.  Now  I  weigh  12  st.  4  lbs.,  all  healthy  substantial  stuff.  I 
am  extremely  obliged  to  you  for  the  interest  you  are  taking  in  my  wellbeing,  and 
infinitely  grateful  to  you.  There  is  not  the  slightest  doubt  in  my  mind  that  if  I 
had  not  consulted  you  when  I  did,  I  should  not  have  lived  another  two  months." 

Recorded  in  full  in  the  "  Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  17S. 

CASE  XXIV.  —  Typical  Myxcedema;  Rapid  Disappearance  of  All  the  Symp- 
toms under  Thyroid  Feeding. 

Male,  aged  36,  married,  consulted  me  on  14th  November  1894,  suffering 
from  typical  myxcedema.  Though  a  medical  man,  the  patient  was  surprised 
when  I  told  him  without  asking  any  questions  that  he  was  suffering  from 
myxcedema. 

Duration.- — 6  years. 

Apparent  cause. — None. 

Present  condition. — The  patient  is  a  tall,  big-made  man.  He  weighs  16  st. 
7  lbs.;  he  has  increased  rapidly  in  weight  of  late.  Three  months  ago  he  only 
weighed  15  st.  His  appearance  is  most  characteristic.  His  face  is  broad  and 
round  (moon-shaped);  the  lips  are  very  thick;  the  lower  lids  are  markedly 
swollen  (bags  of  fluid  beneath  the  eyes);  a  pink  blush  is  present  on  each  check; 
the  eyebrows  and  hair  of  the  head  are  scanty;  the  skin  of  the  face  has  a  dingy 


MYXCEDEMA.  36 1 

yellow  colour.  The  hands  are  very  broad  and  large;  the  feet  and  legs  and  body 
generally  swollen.  No  fatty  swellings  are  present  above  the  clavicles.  The 
tongue  is  very  large;  the  throat  cedematous ;  the  speech  thick  and  slow.  The 
skin  is  very  harsh  and  dry;  the  patient  states  that  he  never  sweats,  and  that  he 
feels  the  cold  intensely;  his  hands  are  always  icy  cold.  The  temperature 
is  subnormal.  He  feels  so  debilitated  that  he  can  hardly  walk;  his  mental 
power  and  memory  are  markedly  impaired ;  he  feels  unfit  for  exertion  either  of 
body  or  mind.  He  says  that  he  is  always  dreadfully  sleepy;  he  can  hardly 
keep  his  eyes  open  when  he  is  doing  his  rounds;  whenever  he  gets  into  his  gig 
he  drops  off  to  sleep.  The  appetite  is  poor;  the  bowels  regular.  The  abdomen 
measures  at  the  umbilicus  38  in. ;  the  chest,  at  the  level  of  the  nipples,  37  in. ; 
the  neck,  round  the  middle,  17  in.  He  is  short  of  breath  on  exertion,  and 
frequently  suffers  from  palpitation.  On  waking  "he  always  feels  a  tremendous 
sensation  of  oppression  in  the  region  of  the  heart."  He  wakes  up  several 
times  through  the  night  with  this  horrible  feeling  of  oppression,  and  great 
difficulty  of  breathing.  On  physical  examination,  the  heart  appeared  to  be 
normal.  A  specimen  of  urine  passed  in  my  consulting-room  was  of  specific 
gravity  1010  ;  it  contained  a  very  decided  quantity  of  albumen,  but  no  sugar  or 
casts.  I  may  here  say  that  the  albumen  was  merely  temporary,  and  only 
present  after  meals.  Many  specimens  were  subsequently  examined.  The 
thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — Very  sleepy,  especially  when 
driving  in  his  gig  ;  frequent  palpitation  ;  on  waking,  he  always  feels  "  a 
tremendous  sensation  of  oppression  in  the  region  of  the  heart";  he  wakes  up 
several  times  through  the  night  with  this  horrible  feeling  of  oppression,  and 
great  difficulty  of  breathing;  heart  normal. 

Thyroid  treatment  commenced  15th  November  1894. 
Preparation  and  Dose. — Dried  extract;   1  to  3  tabloids  daily. 
Immediate  results  of  treatment. — Rapid  disappearance  of  the  myxcedematous 
symptoms;  maximum  loss  of  weight  during  the  treatment  2  st. 
Subsequent  progress. — The  patient  has  continued  quite  well. 
On  12nd  March  1895  (four  months  after  the  commencement  of  the  treatment) 
he  wrote  me  :— "The  truth  is,  life  seems  and  feels  quite  a  different  thing  now. 
When  I  compare  myself  now  with  what  I  was  when  I  left  off  work,  I  am  indeed 
a  different  man.     I  am  taking  a  tabloid  every  other  night  at  bedtime,  and  am 
taking  as  much  care  of  myself  as  possible.     I  have  ceased  to  look  for  and  expect 
swelling  of  my  legs,  and  am  not  short  of  breath  now.     I  stood  the  intense  cold, 
which  we  have  recently  had,  as  well  as  my  neighbours,  I  think;  and  where  I 
was  staying  we  had  for  some  time  a  register  of  130  below  zero.     My  feet  and 
hands  skinned  freely.     My  hair  is  now  as  thick  as  ever  it  was,  and  I  do  not 
feel  the  cold  now.     In  fact,  I  feel  quite  well— better  and  different  from  what  I 
have  been  for  years.     When  I  resumed  work,  many  people  did  not  know  me. 
I  feel  very  grateful  to  you  for  putting  me  in  the  way  of  wellbeing." 

On  \st  March  1898,  the  patient  again  wrote  :— "  I  am  well,  and  enjoy  life 
and  active  work— night  or  day,  and  I  have  plenty  of  both.  I  drive  without 
unduly  feeling  the  cold  as  I  used  to.  and  I  cycle  a  lot  and  enjoy  it.  Life  is  one 
long  pleasure  after  previous  years  of  illness.  The  struggle  was  something 
fearful  when  I  look  back  upon  it.  Perhaps  I  am  a  trifle  heavy— in  weight  I 
mean — but  I  am  convinced  it  is  not  myxcedematous  swelling,  simply  obesity. 
I  take  one  five-grain  tabloid  of  Burroughs  &  Wellcome  every  night." 
Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  181. 


362  DISEASES   OF   THE    BLOOD   GLANDS. 

CASE  XXV. — Typical  Myxcedema  Treated  by  Thyroid  Extract;  Large  Dose 
Required  to  Produce  the  Full  Therapeutic  Effect;  Disappearance  of  the 
Myxedematous  Symptoms;  No  Increase  in  the  Amount  of  Urine  under 
the  Treatment. 

Female,  aged  $3,  married,  no  children,  admitted  to  the  Edinburgh  Royal 
Infirmary,  19th  November  1894,  suffering  from  typical  myxcedema. 

Duration. — 3  years. 

Apparent  cause. — None. 

Condition  on  Admission. — Height,  5  ft  14  in.;  weight,  12  st.  Most  of  the 
characteristic  symptoms  of  myxcedema  are  well  developed.  The  body  is  bulky; 
the  face  is  swollen;  the  lips  are  full,  thick,  elastic,  and  of  a  bluish  colour;  the 
eyelids  are  swollen,  a  faint  pink  blush  is  present  on  each  cheek;  the  skin  of  the 
forehead  is  pigmented ;  the  tongue  is  large  and  thick,  and  the  buccal  mucous 
membrane  and  uvula  cedematous.  The  abdomen  is  much  swollen ;  the  hands 
are  much  larger  than  formerly  (the  patient  states  that  she  is  now  unable  to  get 
gloves  sufficiently  large  to  fit  her) ;  she  says  that  she  is  unable  to  make  fine 
movements  with  the  fingers  because  of  the  feeling  of  stiffness  and  swelling. 
There  is  no  difficulty  in  swallowing,  but  she  states  that  she  occasionally  feels  an 
obstruction  at  the  back  of  the  throat;  the  articulation  is  slow,  monotonous,  and 
thick ;  there  is  no  loss  of  hair  (it  is  abundant  and  dark  on  the  scalp).  The  skin 
is  exceedingly  rough  and  dry;  on  the  forearms  it  is  so  rough  that  on  touching 
it  one  is  reminded  of  a  piece  of  sandpaper;  the  patient  says  that  since  her 
illness  commenced  she  has  only  once  perspired,  and  that  was  after  a  heavy 
day's  washing,  in  a  hot,  moist  wash-house.  The  palms  of  her  hands  are  the 
only  parts  which  are  moist.  She  feels  the  cold  much  more  intensely  than  she 
used  to  do;  the  temperature  is  subnormal  (97°).  Elastic  swellings  are  present 
above  the  clavicles.  The  patient  complains  of  a  numb  feeling  in  the  fingers, 
but  the  objective  sensibility  to  touch,  pain,  heat,  and  cold  is  unimpaired.  She 
often  complains  of  a  frontal  headache.  She  thinks  slowly.  Her  memory  has 
become  impaired.  The  patient  has  not  noticed  that  she  is  worse  in  winter  than 
in  summer.  The  mucous  membranes  are  well  coloured  ;  the  haemoglobin  =  66 
per  cent.  The  menstruation  is  regular;  it  is,  and  always  has  been,  profuse. 
The  amount  of  urine  is  scanty;  she  says  that  she  only  makes  water  twice 
during  the  twenty-four  hours,  and  only  passes  a  small  quantity  at  a  time.  The 
specific  gravity  is  1018.  It  deposits  a  thick  cloud  of  mucus,  but  contains  no 
albumen  and  no  sugar.  The  urea  was  estimated  every  day;  the  amount  varied 
from  4  to  6  grs.  to  the  oz.  The  heart  sounds  are  weak  ;  the  pulse  slow  (63  per 
minute);  tension  good.  The  appetite  is  fair;  digestion  good ;  no  constipation. 
The  thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — Patient's  knee  excised  for  "  white 
swelling"  in  childhood. 

Family  history. — Two  sisters  deaf-mutes. 

Thyroid  treatment  commenced  13th  December  1894. 

Preparation  and  Dose. — B.  &  W.'s  solid  extract ;  one  tabloid  (gr.v.),  gradually 
increased  to  14  tabloids  (70  grs.)  per  diem.     Strychnine. 

Immediate  results  of  treatment. — Sickness,  vomiting,  loss  of  appetite,  furred 
tongue,  severe  frontal  headache,  large  deposit  of  mucus  in  urine,  profuse  per- 
spiration, rise  of  temperature  and  pulse,  slight  jaundice,  disappearance  of 
myxcedematous  symptoms,  desquamation  of  skin,  large  deposit  of  urates  in 
urine,  no  increase  of  the  amount  of  urine. 

Date  of  discharge. — 24th  January  1895  ;  the  myxedematous  symptoms  have 


MYXGEDEMA.  363 

completely  disappeared;  her  appearance  has  quite  changed;  she  says  she  feels 
like  a  new  person — "so  much  more  active."  Maximum  loss  of  weight  during 
the  treatment,  2  st. 

After  her  discharge  from  the  Infirmary  she  continued  to  take  the  thyroid 
regularly  for  more  than  a  year,  and  during  the  whole  of  this  time  kept  well. 
She  then  discontinued  the  drug  for  several  months  and  gradually  fell  back,  all 
the  old  symptoms  returning. 

During  May,  June  mid  July  1897  she  was  as  bad  as  ever  and  confined  to 
bed  for  the  greater  part  of  the  day.  At  the  end  of  July,  she  again  commenced 
the  thyroid,  at  first  3,  then  4  tabloids  daily;  the  symptoms  rapidly  disappeared, 
and  since  then  she  "has  been  in  splendid  health,  better  than  ever  since  her 
illness  commenced  six  years  ago." 

Seen  8th  April  1898. — She  looks  remarkably  well  ;  there  is  absolutely  no 
appearance  of  myxcedema.  She  states  that  since  the  end  of  July  she  has  been 
in  splendid  health.  She  is  now  taking  two  tabloids  daily  ;  one  does  not  seem 
to  be  sufficient.  She  is  able  to  do  all  her  housework  (she  had  not  done  this  for 
three  years  before  admission  to  the  Infirmary) ;  she  does  not  feel  the  cold;  she 
sweats  naturally  and  feels  vigorous  and  strong. 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  152. 

CASE  XXVI. —  Typical  Myxedema :  Complete  Disappearance  of  All  the  Myxe- 
dematous Symptoms  wider  Thyroid  Treatment. 

Female,  aged  42,  widow,  four  children,  seen  in  consultation  on  nth  March 
1895,  suffering  from  typical  myxcedema. 

Duration. — 3  years. 

Apparent  cause. — None. 

Present  condition. — The  patient  complains  of  great  languor  and  debility,  of 
loss  of  memory,  and  extreme  sensitiveness  to  cold.  She  is  somewhat  anaemic. 
Her  appearance,  she  says,  is  so  much  altered  that  many  of  her  friends  and 
acquaintances  have  failed  to  recognise  her  when  she  meets  them.  She  used  to 
have  very  fine  features.  The  skin  of  the  face  has  a  yellow  tinge ;  there  is  no 
pink  blush  on  the  cheeks.  Her  face  is  now  decidedly  puffy-looking,  almost  twice 
as  full,  she  says,  as  it  used  to  be;  the  lower  lip  is  thick,  the  tongue  much  larger 
than  it  used  to  be.  There  are  fatty  swellings  above  the  clavicles.  The  hands 
and  feet  are  also  considerably  swollen.  The  abdomen  is  markedly  enlarged. 
The  speech  is  characteristically  thick.  She  says  that  her  memory  is  much 
impaired,  that  she  always  feels  sleepy,  and  that  she  is  always  worse  in  cold 
weather ;  she  feels  the  cold  intensely ;  during  the  whole  of  last  summer  she  had 
to  wear  her  fur  cloak  in  addition  to  her  winter  flannels,  and  yet  she  never  could 
get  warm;  the  temperature  is  subnormal.  The  skin  is  very  harsh  and  dry,  and 
the  patient  has,  for  the  last  three  years,  ceased  to  sweat.  Hair  much  thinner 
and  darker  in  colour.  The  pulse  is  slow,  56  per  minute ;  the  temperature  sub- 
normal. The  appetite  poor ;  bowels  constipated.  The  urine  does  not  contain 
albumen  ;  amenorrhcea  for  two  years.     The  thyroid  gland  cannot  be  felt. 

Noteworthy  and  exceptional  symptoms. — Since  her  illness  commenced  her 
hair  has  become  black;  it  used  to  be  brown;  the  change  was  so  great  that  her 
brother  thought  she  was  dyeing  it.  Menstruation  returned  under  the  treatment. 
After  the  myxcedematous  symptoms  were  removed  became  melancholic. 

Thyroid  treatment  commenced  3rd  March  1895. 

Preparation  and  Dose. — Liquid  extract  (D.  &  F.'s)  3i.  (=1  of  a  gland)  daily, 
afterwards  increased  to  oiii.  daily. 


364  DISEASES   OF   THE   BLOOD   GLANDS. 

Immediate  results  of  treatment.  —  Marked  and  rapid  improvement ;  free 
desquamation. 

Subsequent  progress. — On  16I/1  May  1895,  the  patient  called  to  see  me  and  I 
did  not  recognise  her.  She  said  that  she  felt  a  different  being;  before  the  treat- 
ment was  commenced  she  was  unable  to  do  anything;  her  memory  and  mental 
powers  were  so  much  impaired  that  in  the  course  of  four  weeks  she  was  unable 
to  get  through  the  first  volume  of  a  three-volume  novel ;  she  could  not  remember 
what  she  had  read,  or  where  she  had  left  off.  Now  her  memory  and  mental 
powers  are  quite  as  active  and  alert  as  they  ever  were.  She  has  read,  she  says, 
a  large  number  of  books  of  all  kinds  during  the  past  month  or  six  weeks,  and 
remembers  what  she  reads.  She  was  advised  to  protect  herself  from  cold  and  to 
take  1  tabloid  (5  grs.  of  the  dried  extract)  daily. 

i~,th  December  1895. — For  the  past  two  or  three  months  the  patient  has  been 
in  a  very  depressed  condition  of  mind,  taking  a  very  morbid  view  of  things, 
saying  she  is  tired  of  life,  etc. — she  is  in  fact  in  a  condition  of  marked  melan- 
cholia. The  myxcedematous  symptoms  have  completely  disappeared;  she  per- 
spires very  freely  on  the  least  exertion;  she  continues  to  take  5  grs.  of  thyroid 
extract  daily.  A  change  of  scene,  with  proper  nursing,  and  a  course  of  tonics 
were  prescribed.     This  treatment  was  quite  successful. 

On  6th  April  1898,  her  medical  adviser  wrote  me  : — "Patient  is  very  well 
indeed  in  every  respect.  I  have  not  seen  her  professionally  for  a  long  time. 
The  other  day,  however,  she  told  me  that  she  still  continues  to  take  one  5-grain 
tabloid  daily;  if  she  omits  it  she  does  not  feel  well." 

Recorded  in  full  in  the  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  187. 


CASE  XXVII. —  Typical  Myxedema  of  the  Atrophic  Form;  Great  Prostration 
Produced  by  the  Thyroid  Treatment. 

Female,  aged  50,  married,  three  children,  seen  in  consultation  14th  May 
1895,  suffering  from  advanced  atrophic  myxcedema. 

Duration. — 12  years. 

Apparent  cause. — None.  Ten  years  ago  she  lost  a  good  deal  of  blood  after 
the  pulling  of  a  tooth  ;  this  aggravated  the  condition,  which  seems  to  have 
increased  rapidly  afterwards.  She  ceased  to  menstruate  three  years  ago.  For 
some  time  previously  she  suffered  from  profuse  menorrhagia. 

Present  condition. — The  patient's  appearance  is  so  typical  that  I  recognised 
the  condition  at  the  first  glance,  without  having  asked  her  any  question.  The 
skin  of  the  face  is  of  a  clingy  yellow  colour ;  there  is  a  pink  blush  on  the  cheeks  ; 
the  hair  on  the  scalp  is  very  thin,  and  the  scalp  is  covered  with  dirty  scales  and 
crusts.  She  is  somewhat  anaemic.  There  is  slight  puffiness  under  the  eyes,  and 
the  lower  lip  is  a  little  full,  elastic-feeling,  and  blue  in  colour;  but  the  myxcede- 
matous swelling  of  the  face  is  very  slight,  and  there  is  no  swelling  of  the  hands 
or  feet.  There  are  no  elastic  swellings  above  the  clavicles.  The  skin  is  remark- 
ably harsh  and  dry;  the  face  is  very  much  wrinkled.  The  patient  says  that  she 
never  sweats,  that  she  is  very  sensitive  to  cold,  and  that  she  is  very  much  worse 
during  the  cold  weather;  she  stood  the  intense  cold  of  the  past  winter  very  badly, 
and  has  been  much  worse  since.  Her  appetite  is  very  poor;  the  bowels  are  con- 
stipated. The  temperature  is  subnormal ;  pulse  72;  heart's  action  weak.  The 
speech  is  highly  characteristic,  slow  and  thick;  the  patient  often  feels  a  choking 
sensation  in  the  throat.  The  skin  of  the  fingers  is  remarkably  dry,  the  nails  very 
small  and  narrow.     The  memory  is  very  much  impaired  ;  the  patient  is  very 


MYXCEDEMA.  365 

slow  in  her  mental  processes  as  well  as  in  her  movements,  and  at  times  is  very 
depressed.  She  sleeps  badly;  often  has  headache ;  complains  of  numbness  in 
hands  and  feet.  The  urine  is  free  from  albumen.  The  thyroid  gland  could  not 
be  felt.  The  condition  of  this  patient,  both  physical  and  mental,  reminded 
me  strongly  of  Case  XI.  ;  and  it  is  very  interesting  to  note  that  both  of  these 
patients  were  peculiarly  susceptible  to  the  action  of  the  remedy. 

Noteworthy  and  exceptional  symptoms. — Little  myxcedematous  swelling,  but 
all  the  other  symptoms  of  the  disease  very  marked ;  face  and  hands  wrinkled ; 
mental  depression  ;  marked  susceptibility  to  thyroid  extract. 

Thyroid  treatment  commenced  15th  May  1895. 

Preparation  and  Dose. — Dry  extract;  five  grains  and  then  ten  grains  daily. 
The  latter  dose  upset  the  stomach  and  produced  great  depression  and  debility; 
had  to  be  stopped  for  a  time.  On  4m  June,  resumed  the  remedy,  1  tabloid 
(gr.  v.)  at  first  every  third  and  subsequently  every  day. 

Immediate  results  of  treatment. — Gradual  and  marked  improvement. 

Subsequent  progress. — On  8t/i  April  1898,  the  patient  called  to  see  me 
looking  very  much  better,  brighter  and  younger.  She  told  me  that  since  the 
treatment  was  commenced  three  years  ago  she  has  been  on  the  whole  very  well 
a  great  deal  stronger,  more  active  and  mentally  brighter  than  she  had  been  for 
10  or  12  years.  The  pink  blush  on  the  cheeks  has  disappeared,  the  face  is  much 
less  wrinkled;  the  scalp  is  still  scurfy,  the  skin  still  rather  harsh  and  dry.  She 
no  longer  feels  the  cold.  She  continues  to  take  2  tabloids  (10  grains  of  the 
extract)  daily;  she  is  much  less  susceptible  to  the  remedy  than  when  the  treat- 
ment was  commenced.  On  several  occasions  during  the  past  three  years  she 
has  discontinued  the  remedy  for  a  few  weeks  at  a  time ;  but  always  had  to 
resume  it  in  the  course  of  a  short  time  as  she  soon  began  to  notice  a  return  of 
the  myxcedematous  symptoms  (weakness,  coldness,  increased  bulk  of  the  body, 
roughness  of  the  skin),  etc. 

Recorded  in  full  in  the  "  Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  190. 


CASE  XXVIII. — Acute  Myxoedema  with  Marked  Symptoms  of  'Mental  Depres- 
sion ;  Suicide  by  Jumping  out  of  Window. 

Female,  aged  30,  married,  three  children,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  16th  November  1895,  suffering  from  myxoedema  and  mental 
depression. 

Duration. — 4  months. 

Apparent  cause. — Grief  due  to  the  sudden  death  of  her  sister.  Patient  is 
naturally  nervous  and  has  been  at  times  depressed  mentally.  Since  her  marriage 
seven  years  ago,  has  suffered  a  good  deal  from  headaches.  Was  confined  five 
months  ago;  labour  easy  and  no  loss  of  blood;  recovered  well.  She  was  in  her 
usual  state  of  health  four  months  ago,  when  she  suddenly  lost  her  sister,  became 
very  depressed,  and  has  since  developed  the  symptoms  from  which  she  now 
suffers  (myxoedema).  Has  become  much  weaker,  body  more  bulky,  face 
heavy  and  swollen,  colour  yellow;  speech  thick;  appetite  poor;  mentally  very 
depressed. 

Present  condition. — Body  bulky;  facial  appearance  highly  characteristic;  face 
and  eyelids  swollen;  skin  of  face  yellow  coloured;  pink  blush  on  cheeks;  eye- 
brows scanty  and  elevated;  forehead  wrinkled  transversely;  lower  lip  swollen; 
tongue  and  throat  swollen;  complains  of  a  choking  sensation  in  throat;  hair 
coming   out,  very  brittle   and  dry;  neck  thick;  no  supraclavicular  swellings; 


2,66  DISEASES   OF   THE    BLOOD   GLANDS. 

hands  thinner;  feet  not  enlarged  or  swollen ;  legs  slightly  swollen ;  abdomen 
swollen  and  large.  Skin  dry  and  harsh ;  absence  of  sweating ;  temperature 
subnormal ;  complains  of  feeling  cold ;  very  sensitive  to  cold.  Speech  charac- 
teristically thick ;  memory  very  much  impaired  ;  frequent  headache  ;  great 
mental  depression  ;  sleeps  badly.  Appetite  very  poor  ;  bowels  constipated  ; 
pulse  72  ;  no  visceral  disease ;  urine  normal ;  has  not  menstruated  since  last 
pregnancy.     Thyroid  cannot  be  felt. 

Result. — The  patient  was  observed  and  the  diet  and  bowels  carefully  regulated 
for  the  first  few  days  after  her  admission  to  hospital,  prior  to  the  commence- 
ment of  the  thyroid  treatment.  At  times  she  was  depressed,  at  other  times  more 
bright  and  natural.  On  20th  November,  while  the  nurses  were  engaged  at  the 
other  end  of  the  ward,  she  got  out  of  bed,  opened  the  window  and  jumped  out. 
Both  legs  were  fractured,  and  she  received  severe  internal  injuries  from  which 
she  died  in  the  course  of  twenty-four  hours. 

Post-mortem  examination  not  allowed. 


CASE  XXIX. —  Typical  and  Advanced  Myxcedema ;  Complete  Disappearance 
of  the  Myxedematous  Symptoms  under  Thyroid  Treatment. 

Female,  aged  64,  married,  ten  children,  seen  in  consultation  on  1st  April 
1896. 

Duration. — 3  years. 

Apparent  cause. — The  symptoms  were  first  noticed  after  an  attack  of 
influenza. 

Present  condition. — The  patient,  who  is  naturally  a  big  stout  woman,  com- 
plains of  a  feeling  of  excessive  exhaustion  and  debility,  of  a  sensation  of  cold- 
ness, and  of  loss  of  memory.  The  body  as  a  whole  is  markedly  large  and 
swollen ;  her  movements  are  ponderous  and  slow ;  the  face  is  very  full  and 
moon-shaped ;  the  lower  eyelids  are  puffy  and  swollen  ;  the  skin  of  the  face  is 
of  a  dingy  yellow  colour  ;  there  is  no  pink  blush  on  the  cheeks  ;  the  lower  lip  is 
markedly  swollen  and  slightly  blue ;  the  hands  and  feet  are  large  and  broad  ; 
the  abdomen  is  large;  the  tongue  is  considerably  enlarged;  the  scalp  is  almost 
destitute  of  hair  and  thickly  encrusted;  the  eyebrows  are  very  scanty;  supra- 
clavicular swellings  are  very  marked.  The  skin  is  harsh  and  dry;  the  patient 
says  that  she  never  sweats;  the  temperature  is  subnormal  (95°);  pulse  66. 
The  articulation  is  characteristically  slow  and  thick;  the  memory  is  very 
markedly  impaired  and  cerebration  very  slow;  she  sleeps  well.  The  appetite 
is  poor;  the  bowels  constipated.  The  urine  is  normal.  The  thyroid  gland 
cannot  be  felt. 

Thyroid  treatment  commenced  29th  March  1896. 

l}r-eparation  and  Dose.— Five  grains  of  the  dried  extract  once  a  day,  in- 
creased for  a  few  days  to  ten  grains  (but  this  dose  was  too  large,  it  produced 
extreme  debility);  strychnine  and  digitalis. 

Immediate  result. — Marked  and  rapid  improvement.  In  the  course  of  a  few 
weeks,  the  myxedematous  symptoms  completely  disappeared  and  the  hair 
began  to  grow. 

Subsequent  progress. — The  patient  continues  well. 

On  2%th  May  1898,  her  doctor  wrote  me: — "She  is  very  well,  lively  and 
intelligent,  able  to  go  about  and  do  her  household  duties  ;  skin  moist,  hair  well 
grown.     She  continues  to  take  one  five-grain  tabloid  daily.'"' 


MYXCEDEMA.  367 

CASE  XXX. — Myxcedema;  Disappearance  of  7110s t  of  the  Myxedematous 
Symptoms  tender  Thyroid  Extract. 

Female,  aged  32,  assistant  in  a  shop,  single,  admitted  to  the  Edinburgh 
Royal  Infirmary  on  31st  January  1897. 

Duration. — 4  years. 

Apparent  cause. — None.  Three  years  ago  was  in  hospital  under  Dr  Bram- 
well's  care  suffering  from  acute  eczema.  At  that  time  her  cheeks  were  very 
pink  in  colour,  but  the  presence  of  myxcedema  was  not  suspected.  It  is  in- 
teresting, however,  to  note  that  the  eczema  was  treated  and  got  well  under  the 
administration  of  large  doses  of  thyroid  extract  (gradually  increased  from  one 
to  fourteen  tabloids  =  70  grains  of  the  dried  extract,  daily) ;  and  it  seems 
probable  that  the  myxcedema  had  been  gradually  coming  on  for  at  least  a  year 
previously. 

Condition  on  admission. — Patient  complains  of  debility,  swelling  and  heavi- 
ness of  the  eyelids,  and  flushings  of  the  face.  The  body  is  bulky;  the  abdomen 
is  moderately  swollen.  The  face  is  full  and  swollen  looking.  The  flushings 
occur  very  frequently;  they  are  usually  worse  in  the  after-part  of  the  day  or 
•after  eating;  she  feels  as  if  the  blood  were  rushing  to  her  cheeks,  which  feel 
hot;  the  feet  become  cold  and  the  cheeks  burning;  the  forehead,  nose  and 
chin  are  not,  she  says,  affected.  The  flushings  do  not  appear  to  have  any 
relationship  to  menstruation.  The  skin  of  the  face  is  thin  and  translucent 
looking,  yellowish  (creamy)  in  colour;  the  cheeks  are  uniformly  tinted  of  a 
bright  pink  colour;  the  eyelids  are  swollen,  the  eyebrows  raised,  the  forehead 
transversely  wrinkled  ;  the  eyes  partly  closed  as  if  the  lids  could  not  be  raised  ; 
the  tongue  is  large,  the  lips  are  not  swollen ;  there  are  no  supraclavicular  swell- 
ings; the  hands  are  square  and  spade-shaped  ;  the  ends  of  the  fingers  are  very 
square  ;  the  nails  furrowed  transversely,  very  brittle  and  apt  to  crack  ;  the  feet 
appear  to  be  normal.  The  eyebrows  are  scanty;  hair  of  head  scanty,  coarse 
and  dry;  no  scabs  on  the  scalp;  skin  very  rough,  dry,  and  inclined  to  be  scaly; 
the  palms  are  particularly  dry,  fissured  and  cracked.  The  patient  never  sweats ; 
she  feels  the  cold  very  much ;  suffers  much  from  cold  hands  and  feet ;  the 
temperature  is  subnormal.  The  voice  is  rough,  and  the  articulation  very  slow 
and  thick.  Memory  is  much  impaired;  her  mental  processes  are  all  slow;  she  is 
very  slow  in  replying  to  questions;  she  is  more  easily  irritated  than  she  used  to 
be.  Appetite  poor;  bowels  regular;  menstruation  usually  regular  in  time,  but 
very  scanty  and  pale.  Some  anaemia.  Urine  normal.  Pulse  slow,  44  per  minute. 
Thyroid  gland  cannot  be  felt. 

Thyroid  treatment  commenced  12th  February. 

Preparation  and  Dose. — Thyrocol ;  at  first,  one  grain  three  times  daily, 
subsequently  increased  to  twelve  grains  three  times  daily,  it  produced  little 
effect  except  intense  headache  and  vomiting.  On  20th  February,  dry  thyroid 
extract  substituted;  at  first,  five  grains  three  times  daily,  gradually  increased  to 
thirty  grains  (on  28th  February)  three  times  daily.  This  close  was  continued 
till  25th  March,  when  the  dose  was  reduced  to  fifteen  grains  three  times  daily; 
on  29th  March,  the  thyroid  was  stopped  for  several  days;  five  grains  daily  were 
subsequently  given. 

Immediate  results  of  the  treatment. — The  thyrocol  produced  intense  head- 
ache and  vomiting.  Under  increasing  doses  of  the  dried  extract  the  myxce- 
dematous  symptoms  gradually  disappeared;  the  temperature  and  pulse  rose; 
the  skin  became  moist  and  less  rough ;  the  swelling  of  the  face  disappeared  ;  the 
flushing  and  injection  of  the  face  diminished;  the  patient  lost  16  lbs.  in  weight. 


368  DISEASES   OF   THE    BLOOD   GLANDS. 

On  ^oth  March  1897  the  patient  was  discharged. 

Subsequent  progress. — Continues  well. 

On  8th  April  1898,  she  stated  that  she  has  been  keeping  well  ever  since  her 
discharge  and  has  been  able  to  follow  her  employment  (assistant  in  a  shop). 
She  feels  much  stronger;  but  has  not  perspired  since  the  hot  weather  of  last 
summer  ;  her  hair  has  not  grown  much  ;  the  skin  is  still  harsh  and  dry  ;  the 
bright  pink  discoloration  of  the  cheeks  is  still  present  (but  she  was  always 
very  highly  coloured)  ;  is  sleeping"  well  ;  appetite  and  digestion  good ;  bowels 
regular  ;  menstruation  still  scanty.  Until  lately,  she  took  one  tabloid  (five 
grains  of  the  dried  extract)  every  other  day  :  of  late,  she  has  only  taken  one 
tabloid  every  week,  as  she  thought  it  made  her  ''shaky." 

Remarks. — In  this  case  the  myxedematous  swelling  was  not  very  marked  ; 
the  flushing  of  the  face  was  very  intense  ;  the  roughness  and  dryness  of  the 
skin  very  great.  Large  doses  of  the  extract  were  tolerated  and  required. 
Acute  eczema  occurred  in  the  early  stages  of  the  disease. 

CASE  XXXI. — Typical  Myxcedema,  Complicated  with  Ulceration  of 'the  Stomach 
and  Peritonitis. 

Female,  aged  41,  single,  was  seen  in  consultation  on  13th  March  1897, 
suffering  from  incessant  vomiting  and  peritonitis. 

Duration. — 14  years  at  least. 

History  and  apparent  cause. — Her  former  medical  attendant  kindly  gave 
me  the  following  account  of  the  previous  history  of  the  case: — "The  patient 
has  never  been  very  strong  ;  she  was  frequently  absent  from  school  because  of 
illness  ;  at  the  age  of  20  she  suffered  from  anaemia,  ulceration  of  the  stomach 
and  profuse  haematemesis ;  the  myxcedematous  symptoms  developed  some  time 
after  this  (the  exact  date  could  not  be  fixed)  ;  before  the  thyroid  treatment 
was  commenced  (February  1893),  she  was  frequently  confined  to  the  house  for 
months  at  a  time,  and  had  frequent  attacks  of  severe  pain  in  the  stomach  and 
vomiting.     She  was  worse  during  cold  weather. 

Family  history. — Her  mother  died  at  the  age  of  68  of  myxcedema,  of  seven 
years'  duration  ;  her  father  died  at  the  age  of  54  of  apoplexy  ;  three  brothers 
died  at  the  ages  of  28,  \y\  and  12,  respectively,  of  tubercular  meningitis, 
phthisis,  and  tubercular  disease  of  the  glands  ;  one  sister  died  at  the  age  of  21 
of  diabetes  ;  one  brother  is  alive  and  said  to  be  healthy,  he  has  a  full  heavy  face 
suggestive  of ' myxcedema ;  three  sisters  are  alive  and  fairly  healthy.  Before  the 
myxcedematous  patient  was  born,  the  mother,  who  was  very  nervous,  passed 
through  a  severe  mental  strain. 

Symptoms. — All  the  characteristic  features  of  myxcedema  were  present,  the 
mental  symptoms  being  particularly  pronounced. 

Thyroid  treatment  commenced  at  the  end  of  February  1893. 

Preparation  and  Dose. — Ten  drops  of  thyroid  extract  daily ;  subsequently 
increased  to  fifteen  drops. 

Immediate  result. — Rapid  improvement.  On  jyth  May  1893  (eleven  weeks 
after  the  treatment  was  commenced),  the  following  note  was  made  regarding 
her  condition  : — "The  result  has  been  satisfactory,  the  most  marked  improve- 
ment being  mental.  She  sweats  freely  and  does  not  remember  sweating  before 
the  treatment;  the  face  has  become  changed;  the  hair  is  growing  rapidly;  the 
gastric  symptoms  seldom  trouble  her,  and  she  walks  and  goes  up  a  stair  better 
than  she  has  done  for  years ;  the  temperature  is  normal  in  the  morning  and 
down  to  97"  in  the  evening;  the  evening  fall  took  place  when  she  began  to  get 


MYXCEDEMA.  369 

up  for  the  day;  changing  the  time  for  giving  the  thyroid  does  not  raise  the 
temperature  in  the  evening." 

Subsequent  progress  of  the  case. — The  gastric  symptoms  continued  to  recur, 
and  although  the  myxcedema  was  to  a  considerable  extent  kept  in  abeyance  by 
the  thyroid  extract  the  patient  never  got  strong. 

During  the  years  1895  and  1896,  she  continued  to  suffer  from  her  stomach. 
The  menstruation,  which,  prior  to  the  thyroid  treatment,  had  been  too  profuse 
(menorrhagia),  became  irregular  ;  she  frequently  missed  three  periods  at  a  time, 
and  the  menstruation,  when  present,  was  always  scanty. 

During  the  spring  of  1897,  the  patient  on  two  or  three  occasions  vomited 
small  quantities  of  blood. 

Condition  on  13th  March  1897. — The  patient  is  in  a  very  debilitated  condi- 
tion; the  feet  are  swollen  ;  well  marked  myxedematous  symptoms  are  still 
present ;  the  patient  complains  of  feeling  cold  ;  the  skin  is  rough  and  dry  ;  the 
skin  of  the  face  has  a  dingy  yellow  tinge ;  a  pink  blush  is  present  on  the 
cheeks  ;  the  lips,  hands  and  feet  are  swollen  ;  there  are  no  supraclavicular 
swellings  ;  the  hair  is  thin,  but  not  markedly  so  ;  before  the  treatment  the 
patient  was  quite  bald  ;  there  is  no  encrustation  of  the  scalp  ;  the  memory, 
which,  prior  to  the  commencement  of  the  thyroid  treatment,  was  very  bad,  was 
still  somewhat  impaired ;  the  articulation  was  characteristically  thick ;  the 
bowels  were  constipated  ;  the  urine  was  free  from  albumen  ;  the  heart  was 
weak,  but  there  was  no  valvular  disease  ;  no  thyroid  gland  could  be  felt. 

Incessant  vomiting  was  present,  almost  everything  being  rejected  ;  the 
patient  complained  of  intense  pain  and  tenderness  over  the  abdomen,  which 
was  swollen  ;  the  temperature  was  101.6°;  the  pulse  ro8. 

Treatment. — Peptonised  milk  and  ice  by  the  stomach  ;  nutrient  enemata 
and  suppositories  ;  morphia  hypodermically  ;  strychnine  and  strophanthus. 

Result. — The  stomach  symptoms,  though  somewhat  relieved,  continued, 
and  the  patient  died,  apparently  from  subacute  peritonitis  and  exhaustion,  on 
22nd  April  1897. 

Post-mortem  examination. — None. 

CASE  XXXII. —  Typical  Myxcedema;  Rapid  and  Complete  Disappearance  of 
the  Myxedematous  Symptoms  under  Thyroid  Treatment. 

Female,  aged  32,  married,  four  children,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  30th  March  1897. 

Duration. — 2  years. 

Apparent  cause. — The  symptoms  began  to  develop  after  the  birth  of  her  last 
child  ;  was  quite  well  before  this  ;  the  labour  was  easy,  and  was  not  attended 
with  any  excessive  loss  of  blood;  for  five  days  after  her  confinement  she  suffered 
severe  pain  in  the  lower  part  of  the  abdomen  ;  was  up  on  the  fourteenth  day, 
but  feeling  very  weak. 

Present  condition. — Patient  complains  of  debility,  mental  depression,  severe 
headache,  a  feeling  of  cold,  etc.  Looks  considerably  older  than  her  age,  and  is 
somewhat  anaemic.  The  body  as  a  whole  is  bulky ;  the  facial  appearance  typical ; 
face  full  and  slightly  swollen;  skin  slightly  yellow  in  tint ;  a  pink  blush  on  the 
cheeks;  lower  lip  full,  tense,  and  slightly  purple  in  colour;  tongue  not  large;  throat 
not  swollen;  ears  natural  ;  no  supraclavicular  swellings;  hands  and  feet  broad 
and  large ;  abdomen  large  and  pendulous  ;  eyebrows  elevated  and  scanty ;  fore- 
head transversely  wrinkled  ;  hair  of  head  very  dry  and  coarse,  but  not  thinner 
than  it  used  to  be ;  scalp  scaly,  but  not  encrusted ;  skin,  except  on  face,  very  dry 

2  A 


370  DISEASES   OF    THE    BLOOD   GLANDS. 

and  rough;  no  sweating;  feels  the  cold  very  much;  worse  in  cold  weather; 
temperature  subnormal ;  complains  of  numbness  of  the  hands  and  feet;  sensation 
delayed  ;  sight  and  hearing  somewhat  impaired  ;  memory  bad  ;  marked  mental 
depression  and  listlessness  ;  voice  rough;  articulation  thick  and  leathery;  knee- 
jerks  normal ;  sleeps  well ;  pulse  slow,  50  ;  appetite  good ;  bowels  slightly  con- 
stipated; urine  normal;  menstruation  regular  in  time,  but  since  the  onset  of 
the  disease  attended  for  the  first  two  days  with  great  pain  in  the  back  and  right 
flank;  no  visceral  disease.     No  thyroid  to  be  felt. 

Thyroid  treatment  commenced  15th  April  1897. 

Preparation  and  Dose. — At  first  the  dried  extract  (maximum  dose  sixteen 
tabloids  =  eighty  grains,  daily);  subsequently  the  raw  gland  (J  of  a  gland  daily, 
subsequently  reduced  to  ^th  of  a  gland). 

Immediate  result. — Little  improvement  under  the  dried  extract ;  marked  and 
rapid  improvement  (rise  in  temperature,  pulse,  and  respirations,  sweatings,  dis- 
appearance of  the  mxycedematous  swelling ;  great  improvement  in  memory  and 
mental  condition,  etc.)  under  the  raw  gland. 

On  24th  May  1897,  the  patient  was  discharged  looking  fifteen  years  younger 
than  before  the  treatment ;  skin  smooth  ;  headache  much  less  frequent  and 
severe ;  the  mental  depression  quite  gone ;  feeling  bright  and  lively,  laughing 
and  talking  continually  ;  voice  and  articulation  natural.  Loss  of  weight  during 
the  treatment  =  15^  lbs. 

Subsequent  progress. — Remains  quite  well. 

Remarks. — Large  doses  of  the  dried  extract  produced  so  little  effect  that 
I  was  disposed  to  think  the  tabloids  were  bad.  The  raw  gland  produced  an 
immediate  and  marked  effect. 


CASE  XXXIII. — Imperfectly  Developed  Myxaedema  ;  Marked  Improvement 
under  Thyroid  Treatment. 

Female,  aged  48,  single,  lady's  maid,  admitted  to  the  Edinburgh  Royal 
Infirmary  on  19th  May  1897.     Weight  =  7  stone  85  lbs. 

Duration. — \\  months. 

Apparent  cause. — None. 

Family  history. — Two  brothers  died  of  phthisis. 

Present  condition. — Patient  complains  of  debility,  palpitation,  shortness  of 
breath,  a  sensation  of  cold,  and  swelling  of  the  feet.  The  body  as  a  whole  is 
not  swollen  ;  the  face  is  full  and  round  ;  the  skin  of  the  face  markedly  yellow  in 
colour;  a  well-marked  pink  blush  (more  bright  and  diffused  than  in  most  cases 
of  myxaedema)  covers  the  cheeks  and  chin ;  the  upper  eyelids  are  swollen ;  the 
skin  of  the  face  is  thin  and  translucent  looking;  the  lips,  tongue,  throat,  ears, 
hands,  and  abdomen  are  not  swollen ;  the  feet  and  ankles  are  slightly  swollen 
(ordinary  oedema) ;  there  are  no  supraclavicular  swellings  ;  the  thyroid  gland 
cannot  be  felt ;  the  patient  is  extremely  sensitive  to  cold ;  the  temperature  is 
subnormal ;  the  skin  (except  on  the  face)  is  very  harsh  and  dry ;  she  never 
sweats;  the  mouth  and  throat  are  drier  than  formerly;  the  head  is  almost  bald, 
the  hair  having  come  out  since  the  disease  commenced;  the  hair  is  dry  and 
brittle;  the  scalp  is  encrusted;  the  eyebrows  and  eyelashes  are  scanty;  the 
nails  are  brittle  and  cracked ;  the  voice  and  articulation  are  natural ;  the  memory 
is  much  worse  than  it  was  5  months  ago  ;  there  is  considerable  anaemia  and  a  soft 
systolic  murmur  in  the  mitral  area;  the  pulse  is  quick,  100  to  no;  the  appetite 
is  poor;  digestion  f.iir;  bowels  constipated;  the  patient  has  never  menstruated 


MYXCEDEMA.  37 1 

regularly,  and  ceased  entirely  to  menstruate  several  years  ago  ;  the  urine  is 
normal. 

Thyroid  treatment  commenced  on  31st  May  1897. 

Preparation  and  Dose. — Dried  extract,  five  grains,  gradually  increased  to 
twenty-five  grains,  daily  ;  arsenic  ;  strychnine ;  strophanthus. 

Immediate  result. — With  some  ups  and  downs,  the  patient  gradually  im- 
proved, and  was  discharged  from  hospital  on  28th  July  1897. 

On  her  discharge,  the  patient  felt  much  stronger,  more  active,  and  better  in 
•every  way ;  her  face  had  entirely  lost  the  myxoedematous  appearance  ;  skin 
softer  and  more  moist  ;  no  growth  of  hair  ;  temperature  normal ;  pulse,  which 
on  admission  was  quick  (100  to  1 10),  had  fallen  to  60  ;  memory  better.  Loss  of 
weight  during  treatment  =  14-^  lbs. 

Remarks. — A  peculiar  feature  of  this  case  was  the  fall  in  the  pulse-frequency 
during  the  treatment ;  it  did  not  seem  to  be  satisfactorily  accounted  for  by  the 
small  doses  of  strophanthus  which  were  administered. 


B.— CASE  OF  JUVENILE  MYXCEDEMA. 

CASE  XXXIV. — Juvenile  A'Iyxccdcma>;  Complete  Disappearance  of  the  Myxce- 
dematous  Symptoms  under  Thyroid  Treatment. 

Female,  aged  14,  admitted  to  the  Edinburgh  Royal  Infirmary  on  26th  January 
1897,  complaining  of  debility  and  arrested  growth. 

Duration. — At  least  4  years. 

History. — Patient's  birth  was  easy  and  non-instrumental.  Nothing  was 
noticed  wrong  with  her  until  four  years  ago.  She  then  stopped  growing,  and 
has  not  grown  at  all  since.  At  the  age  of  7,  she  had  measles ;  at  the  age  of  12, 
herpes  zoster  (scars  very  marked).  Up  to  the  age  of  10,  she  was  a  well-grown 
and  well-developed  child. 

At  the  age  of  1 1  she  was,  by  the  advice  of  her  medical  attendant,  taken  from 
school  "because  she  was  too  advanced  for  her  age  and  was  not  growing";  she 
was  very  clever  at  her  lessons,  seldom  requiring  to  prepare  them,  and  was  then 
in  the  5th  Standard.  (The  absence  of  any  mental  defect  at  this  date  is  remark- 
able, for  the  myxoedematous  condition  must  have  been  present  in  some  degree 
before  this  time  ;  on  inquiry  it  was  ascertained  that  the  patient  did  not  shed  any 
of  her  milk  teeth  till  the  age  of  11.)  Since  the  arrest  in  her  growth  occurred, 
she  has  lost  all  her  old  energy,  has  given  up  playing,  is  inclined  to  sit  by  the 
fire  and  has  been  very  quiet  and  sedate.  During  the  past  two  years,  her  face 
has  become  puffy  and  swollen,  the  skin  dry ;  she  has  felt  the  cold  very  much, 
has  ceased  to  sweat ;  her  hair  has  come  out.  For  the  past  three  months,  she  has 
complained  of  (?  rheumatic)  pains  in  the  small  of  the  back,  and  in  the  elbow, 
knee,  and  ankle  joints. 

Family  history. — Her  father  and  paternal  grandmother  died  of  phthisis;  a 
sister  died  of  scrofulous  disease  of  the  knee  and  spine  ;  a  brother  takes  fits  ;  a 
maternal  aunt  died  in  an  asylum  from  fits. 

Present  condition. — Height  =  4  ft.  -zh  ins.;  weight  =  4  st.  6|  lbs. ;  temperature 
97°;  pulse  56;  somewhat  anasmic ;  red  corpuscles  =  2,800,000  per  c.mm. ; 
haemoglobin  =  30  per  cent. 

Body  short  and  broad ;  expression  dull  and  heavy ;  face  broad  and  puffy ; 
eyelids  slightly  swollen;  face  pale  ;  very  faint  malar  blush  ;  nose  short  and  thick 


372  DISEASES   OF   THE    BLOOD   GLANDS. 

at  the  tip,  nostrils  wide,  slightly  pug-shaped  ;  lower  lip  slightly  swollen  ;  tongue 
not  specially  large;  ears  small  and  well  shaped;  hands  and  feet  somewhat 
broad  ;  slight  tumefactions  above  the  clavicles  ;  neck  very  thick  ;  the  abdomen 
is  not  specially  large  ;  there  is  no  umbilical  hernia.  Head  large  (circumference 
=  2i?r  inches);  fontanelle  closed;  hair  fairly  thick,  short  and  very  dry;  some 
scurfiness  of  scalp  ;  the  hair  was  cut  nine  months  ago  and  has  not  grown  at 
all  since ;  eyelashes  long  and  thick  ;  eyebrows  scanty.  Teeth : — The  lateral 
incisors  on  the  right  side,  in  both  the  upper  and  the  lower  jaw,  are  reduplicated  ; 
there  is  only  one  molar  tooth  in  each  lower  jaw ;  the  double  teeth  are  rather 
decayed.  The  teeth  which  she  has  at  present  are,  with  the  exception  of  the 
four  upper  and  the  three  lower  incisors,  those  of  the  first  set.  She  had  no  teeth 
of  the  second  set  when  ten  years  old  ;  the  first  tooth  was  shed  when  she  was 
eleven  years  old  ;  the  two  new  upper  incisors  appeared  when  she  was  twelve 
years  old  ;  they  took  a  very  long  time  to  grow  in.  The  skin  is  rough  and  dry 
except  on  the  face ;  she  never  sweats ;  she  feels  the  cold  very  much ;  the  feet 
and  hands  are  often  blue  and  cold.  The  voice  and  articulation  are  normal ;  the 
mental  development  good,  but  the  memory  is  not  nearly  so  good  as  it  used  to 
be  ;  she  sleeps  well.  The  thyroid  gland  cannot  be  felt.  Gait,  motor  functions 
and  sensory  functions  all  normal.  Knee-jerks  active.  Appetite  very  good  ; 
breath  foul;  tongue  coated;  bowels  apt  to  be  constipated.  Urine  normal.  No 
visceral  disease. 

Thyroid  treatment  commenced  12th  February  1897. 

Preparation  and  Dose. — Thyrocol  was  first  given  (one  grain  daily,  increased 
to  three  grains  daily) ;  it  caused  headache  and  sickness  and  had  comparatively 
little  effect  on  the  myxcedematous  condition.  On  10th  February,  the  dried  thy- 
roid extract  was  substituted  ;  at  first,  five  grains  three  times  daily,  gradually 
increased  to  four  tabloids  (20  grains)  three  times  daily,  on  26th  February  ; 
reduced  to  ten  grains  three  times  daily  on  4th  March  ;  five  grains  three  times 
daily  on  24th  March  ;  and  five  grains  twice  daily  on  29/h  March. 

Immediate  results. — Rapid  disappearance  of  the  myxcedematous  symptoms, 
after  the  full  effect  of  the  thyroid  was  obtained  (rise  in  temperature,  sweating, 
growth  of  body  and  hair). 

On  gth  March,  the  patient  had  grown  half  an  inch  in  height,  and  her  hair 
had  grown  one  inch  and  a  half  in  length.     Temperature  990,  pulse  108. 

On  2gth  March  was  discharged.  Height  =  4  ft.  3^  ins.  (a  gain  of  \  in.)  ; 
weight  =  4  st.  (a  loss  of  6|  lbs.). 

Subsequent  progress. — Continues  well. 

On  gth  February  1898  she  was  quite  well ;  height  =  4  ft.  6h  ins.;  weight  =  4  st. 
61  lbs.  (without  clothes);  is  very  bright;  never  feels  the  cold;  sweats  naturally; 
skin  smooth;  hair  growing;  eats  well;  bowels  natural.  Has  lost  one  double 
tooth. 


C—  CASES  OF  SPORADIC  CRETINISM  {Infantile  Myxedema). 

CASE  XXXV '. — Typical  Sporadic  Cretinism;  Rapid  Disappearance  of  All  the 
Myxoedematous  Symptoms  under  Thyroid  Treatment ;  Continued  and 
Progressive  Improvement. 

Female,  aged  8.\,  admitted  to  the  Edinburgh  Royal  Infirmary,  7th  January 

i«93. 

Duration.—  8]  years  ;  symptoms  first  noticed  at  age  of  4  months. 


MYXCEDEMA.  373 

Apparent  cause. —  None.  Labour  difficult  (instrumental)  but  head  not  in- 
jured; when  3^  months  old,  nearly  choked  in  bath;  frightened  by  nurse  at  9 
months  old. 

Family  history.  —  Patient  is  the  eldest  of  four  children  ;  one  died  of  measles; 
the  two  survivors  healthy.  Father  aged  41,  mother  aged  43  ;  both  healthy. 
Father  lame  from  poliomyelitis  anterior  acuta ;  mother  nervous';  four  children 
of  a  sister  of  father  affected  with  Friedreich's  ataxia. 

Present  condition. — Height  =  34^  inches  ;  weight  =1  st.  I2|  lbs. ;  somewhat 
anaemic.  Body  short  and  squat ;  face  swollen,  mouth  large,  nose  pug-shaped, 
eyelids  much  swollen,  skin  translucent  and  ivory-looking;  a  slight  pink  blush 
present  on  the  cheeks;  tongue  not  enlarged;  milk  teeth  present;  neck  short 
and  thick ;  elastic  swellings  above  the  clavicles ;  abdomen  very  large ;  small 
umbilical  hernia;  hands  and  feet  large,  broad  and  short;  back  curved;  a  fine 
growth  of  hair  between  the  shoulders.  Anterior  fontanelle  closed ;  head  covered 
with  a  considerable  quantity  of  dark,  lank,  coarse  hair  ;  scalp  dry  and  encrusted. 
Calves  and  forearms  large,  firm  and  elastic ;  skin  of  palms  and  soles  wrinkled ; 
skin  dry  and  harsh ;  patient  never  sweats  ;  very  sensitive  to  cold;  worse  in  cold 
weather  ;  likes  heat,  and  enjoys  basking  in  the  sun  or  roasting  before  a  hot  fire; 
temperature  subnormal.  Voice  rough  and  hoarse  ;  splendid  sleeper.  Appetite 
poor ;  bowels  obstinately  constipated.  Urine  free  from  albumen  ;  a  mucous 
deposit  sometimes  present.  The  thyroid  gland  cannot  be  felt.  Venous  mottling 
present  on  the  chest,  arms,  abdomen  and  thighs.  Very  dull  and  apathetic; 
never  smiles  or  takes  any  notice  of  what  is  going  on  around  her.  Placed  in 
any  position,  will  remain  for  hours  quiet,  without  making  any  spontaneous 
movement.  Understands  what  is  said  to  her,  recognises  objects,  and  knows 
their  names  ;  her  vocabulary  is  fairly  good,  but  she  seldom  exerts  herself  to 
speak.  Her  mother  says  that  her  intelligence  is  not  much  more  advanced  than 
that  of  a  child  of  three  years  of  age.  General  state  of  nutrition  good  ;  though 
dwarfed,  fat.  Always  passes  urine  in  bed.  When  her  parents  came  to  see  her 
she  took  no  notice  of  them,  and  did  not  answer  them  when  spoken  to.  Pulse 
regular,  80.     Thyroid  cannot  be  felt. 

Thyroid  treatment  commenced  10th  January  1894. 

Preparation  and  Dose. — £th  of  raw  gland,  increased  to  \  on  1 8th  January. 

Immediate  result  of  treatment. — The  first  dose  produced  a  rise  in  tempera- 
ture ;  this  was  soon  followed  by  the  rapid  disappearance  of  the  myxcedematous 
symptoms  ;  rise  in  pulse  ;  sweating  ;  increased  appetite  ;  disappearance  of 
constipation  ;  great  improvement  in  mental  condition. 

\oth  March  1894. — Discharged;  parents  greatly  pleased  with  the  extraor- 
dinary change  in  patient's  condition.  To  take  ten  drops  of  B.  &  M.'s  liquid 
extract,  every  other  day. 

Subsequent  progress. — \st  April. — Very  irritable,  bad-tempered  and  excited; 
dose  of  extract  reduced  to  five  drops. 

2,oth  June  1894. — Height  =  36f  inches  ;  weight  =  2  st.  6J  lbs. 

8th  February  1895. — Quite  well  since  last  note.  Very  lively  ;  skin  smooth  ; 
height  38^  inches. 

wth  May  1895. — Perfectly  well  since  last  note,  and  taking  one  tabloid  every 
other  day.  Began  to  go  to  school  last  September,  and  has  made  fair  progress 
with  her  lessons  ;  is  now  a  lively  child,  active  both  in  body  and  mind  ;  instead 
of  being  sullen  and  quiet,  is  now  irritable  and  often  bad-tempered  ;  appetite  and 
digestion  very  good  ;  bowels  regular  ;  skin  perfectly  natural  ;  still  some  encrus- 
tation of  scalp  ;  hair  long,  silky,  and  quite  healthy. 


374  DISEASES   OF   THE   BLOOD   GLANDS. 

8///  April  1898. — Quite  well  since  last  note;  no  appearance  of  myxcedema; 
umbilical  hernia  gone  ;  skin  moist  and  smooth  ;  hair  long  and  black  ;  perspires 
naturally ;  does  not  feel  the  cold  ;  has  not  been  once  absent  from  school  during 
the  past  two  years  ;  doing  well  at  her  lessons  ;  in  the  2nd  Standard  ;  temper 
rather  peculiar  ;  appetite  good  ;  bowels  regular  ;  height  =  46  inches. 

Both  feet  very  high  in  the  instep  and  short  from  before  backwards  (suggestive 
of  commencing  Friedreich's  ataxia) ;  left  knee-jerk  exaggerated,  right  normal. 

The  height  at  different  dates  was  as  follows: — 29th  June  1890  =  31^  in.; 
19th  March  1891  =  32^  in.  ;  8th  January  1893  (thyroid  treatment  commenced)  = 
34i  in.  ;  13th  February  1893  =  35^  m-  '■>  3otn  June  I893  =  36f  in.  ;  8th  February 
1894  =  38^  in.  ;   nth  May  1895  =  42^  in.  ;  8th  April  1898  =  46  in. 

Recorded  in  full,  "Atlas  of  Clinical  Medicine,"  Vol.  i.,  p.  23  ;  and  "Edin- 
burgh Hospital  Reports,"  Vol.  iii.,  p.  198. 

CASE  XXXVI. — Extreme  Sporadic  Cretinism  in  a  Patient  aged  i6T\  ;  Disap- 
pearance of  the  Myxcedematons  Symptoms  under  Thyroid  Feeding ; 
Increase  in  Height ;   Very  Slight  Improvement  in  the  Mental  Condition. 

Female,  aged  i6T\,  admitted  Edinburgh  Royal  Infirmary,  30th  March  1893. 

Duration. — ?  16  years  or  from  birth.  Nothing  definite,  except  enlargement  of 
tongue  and  mottling  of  skin,  noticed  till  child  was  9  months  old. 

When  3!  years  old,  very  ill  with  "  stoppage  of  the  bowels  " ;  at  5,  had  chicken- 
pox  ;  at  7,  measles  ;  at  8,  whooping-cough  ;  at  10,  scarlet  fever  ;  and  at  12,  a 
large  glandular  abscess  in  neck.  Her  hair,  which  was  previously  pretty  thick, 
began  to  come  out  after  the  scarlet  fever ;  it  has  not  grown  since. 

Apparent  cause. — None. 

Family  history. — Excellent  in  every  way. 

Present  condition. — Though  16  years  of  age,  does  not  look  more  than  2  or 
z\  years  old  ;  height  =  29!  inches  ;  weight  =  2  st.  %\  lbs.  ;  no  anaemia  ;  anterior 
fontanelle  widely  open  (6  x  5^  cm.) ;  stumps  of  first  set  of  teeth  still  present ; 
unable  to  stand ;  can  support  herself  in  a  semi-erect  position  by  leaning  on  her 
chest  and  arms  ;  unable  to  creep  in  the  ordinary  way,  but  pulls  herself  along  for 
a  short  distance  on  her  belly  by  her  arms.  Mental  development  is  completely 
arrested  ;  grunts  and  barks  like  one  of  the  lower  animals,  but  does  not  seem  to 
be  able  to  produce  any  intelligible  articulate  sound  ;  seems  to  have  some  sort 
of  dull  intelligence.     Can  see,  hear  and  taste. 

Looks  more  like  one  of  the  lower  animals  than  a  member  of  the  human 
race,  the  facial  appearance  and  expression  resembling  that  of  a  bull-dog  more 
than  anything  else.  Head  large  in  proportion  to  the  body  ;  mouth  of  enormous 
size,  and  always  open  ;  saliva  frequently  dribbles  away  from  it  ;  cavity  of  mouth 
very  capacious;  lips  very  thick  and  blue;  lower  lip  everted;  tongue  of  enor- 
mous size,  both  in  length  and  breadth,  and  of  a  dark,  purple  colour,  constantly 
projected  between  the  teeth ;  nose  very  small,  sunken,  and  snub-shaped ;  nos- 
trils large,  dilated,  and  set  widely  apart.  Eyes  small  and  bead-like,  partly 
closed  by  cedematous  swelling  of  the  lids.  No  pink  blush  on  the  cheeks  ;  face 
yellow  and  pale  ;  skin  of  the  body  generally  of  a  dingy  yellow  hue  ;  scalp  over 
the  position  of  the  anterior  fontanelle  destitute  of  hair  ;  a  considerable  quantity 
of  coarse,  dry,  shaggy  hair  covers  the  back  and  sides  of  the  head ;  eyebrows 
hardly  perceptible;  eyelashes  in  the  lower  lids  scanty;  slight  blepharitis. 
Belly  large;  an  umbilical  hernia  of  (relatively)  great  size.  Hands  and  feet  very 
broad,  thick  and  wrinkled;  legs,  thighs,  arms  and  forearms  firm;  the  tissues 
infiltrated    with  solid   oedema.      Skin   mottled,   very   harsh   and    dry  ;    patient 


MYXCEDEMA.  375 

never  sweats  ;  several  moles  and  warts,  some  of  them  pigmented,  scattered 
over  the  surface  of  the  body;  sensibility  of  the  skin  seems  normal.  Neck  very 
thick  ;  very  large  elastic  swelling  above  the  clavicles.  Spine  curved  towards 
the  right  ;  left  knee-joint  distorted;  tibiae  bent  as  if  from  rickets.  Appetite 
good,  but  patient  often  vomits;  disagreeable  odour  of  breath;  bowels  very 
costive.  Temperature  subnormal ;  always  worse  during  winter,  somewhat 
better  and  brighter  during  summer.  Pulse  of  normal  frequency.  Urine  con- 
tains a  small  quantity  of  globulin.  Pays  no  attention  to  the  calls  of  nature. 
Sleeps  well.     Thyroid  cannot  be  felt. 

Thyroid  treatment  commenced  ist  April  1893. 

Preparation  and  Dose. — B.  &  M.'s  liquid  extract,  five  drops  daily,  subse- 
quently increased  to  seven  and  ten  drops  (for  a  few  days) ;  afterwards  B.  &  W.'s 
tabloids,  gr.  v.,  every  other  day. 

Immediate  result  of  the  treatment. — Rapid  disappearance  of  the  myxcede- 
matous  swellings,  rise  in  temperature  and  pulse,  skin  less  harsh  and  dry,  loss  of 
3^  lbs.  in  weight,  looks  brighter  and  more  intelligent. 

17th  May  1893. — Discharged,  distinctly  improved. 

Subsequent  progress  of  the  case. — 15///  November  1893  (six  months  after 
the  commencement  of  the  treatment). — Looks  much  bigger  and  older  than  she 
did  three  months  ago.  Before  the  thyroid  treatment  was  commenced  did  not 
look  more  than  2  or  2-|  years  of  age  ;  now  looks  at  least  4  or  5.  Has  grown 
6\  inches  since  ist  April  ;  now  measures  36  inches  in  length.  The  curvature  of 
the  spinal  column  is  much  more  apparent.  Her  father  and  mother  say  that  she  is 
much  brighter  and  more  intelligent.  The  anterior  fontanelle  is  much  smaller 
than  it  used  to  be,  very  firm  and  evidently  being  filled  in  with  bone.  The  hair  has 
grown  over  the  bald  part  of  the  scalp ;  the  eyebrows  are  also  much  thicker, 
stronger,  and  longer.  Has  got  four  new  teeth;  the  legs  are  firmer,  but  still 
very  soft.  Is  able  to  support  herself  on  her  legs  much  better  than  she  used  to 
do,  but  is  still  unable  to  stand  erect  even  with  support.  In  some  respects  the 
patient  does  not  seem  so  well  as  she  was  at  the  end  of  July.  The  skin  is  more 
dry  and  harsh,  the  tongue  is  larger,  and  the  supraclavicular  swellings  are  more 
marked.  The  dose  of  thyroid  was  consequently  increased  from  1  to  1^  tabloids 
every  other  day. 

April  1898. — Since  the  last  note,  there  has  been  little  or  no  improvement  ; 
the  thyroid  has  only  been  very  intermittently  given,  the  parents  being  afraid  of 
the  emaciation  and  depression  which  it  produces. 

The  height  at  different  dates  was  as  follows  : — 3rd  April  1893  (before  thyroid 
treatment  commenced)  =  295  in.  ;  8th  April  1893  =  29!  in.;  7th  June  1893  =  32 
in.;   15th  Nov.  1893  =  36  in.  ;   12th  May  1895  =  37j  in. 

Note. — In  this  case,  in  which  the  disease  was  most  extreme  and  the  patient 
comparatively  advanced  in  age,  one  could  hardly  expect  any  considerable 
degree  of  improvement. 

Recorded  in  full,  "Edinburgh  Hospital  Reports,"  Vol.  hi.,  p.  203. 

CASE  XXXVII. — Typical  Sporadic  Cretinism ;  Rapid  and  Continued  Im- 
provement wider  Thyroid  Treatment. 

Female,  aged  3  years,  seen  in  consultation  13th  March  1893. 

Duration. — 1\  years  ;  the  disease  was  first  noticed  when  the  child  was  8  or 
9  months  old. 

Apparent  cause. — None  ;  born  in  India  ;  birth  easy  ;  two  attacks  of  fever 
in  early  infancy. 


3/6  DISEASES   OF   THE    BLOOD   GLANDS. 

Family  history. — Excellent. 

Present  condition. — Does  not  look  more  than  8  or  9  months  old ;  slightly 
anaemic  ;  anterior  fontanelle  widely  open  ;  no  teeth ;  mouth  large,  usually  open  ; 
lips  thick  and  slightly  bluish  in  tint ;  tongue  very  large,  usually  protruding  between 
the  teeth  ;  face  and  eyelids  puffy  and  swollen ;  skin  translucent  and  waxy  look- 
ing; gums  thick  and  hard;  hands  and  feet  short  and  stumpy;  abdomen  very 
large  ;  small  umbilical  hernia  ;  hair  very  scanty,  but  sufficiently  long  and  soft, 
and  of  a  golden-brown  colour  ;  a  thick  growth  of  fine  downy  hairs,  $  of  an  inch 
in  length,  extends  over  the  forehead  as  far  as  the  eyebrows,  which  have  only 
grown  in  during  the  last  few  months ;  eyelashes  long,  but  somewhat  scanty. 
Temperature  subnormal  ;  skin  soft  and  smooth  ;  sweats  freely  ;  constipation 
very  marked  ;  large  elastic  swellings  above  the  clavicles ;  appetite  small  ; 
general  state  of  nutrition  good  ;  temper  placid  ;  likes  to  be  fondled,  and  strokes 
the  nurse's  face  with  its  hands,  but  this  seems  to  be  the  only  evidence  of  intelli- 
gence ;  sleeps  well;  cannot  say  a  single  word,  not  even  "Ba-ba";  makes  no 
attempt  to  creep  ;  radial  pulse  cannot  be  felt  ;  heart  numbers  96  per  minute. 
Thyroid  cannot  be  felt. 

Thyroid  treatment  commenced  30th  March  1893. 

Preparation  and  Dose. — Ten  drops  of  B.  &  M.'s  liquid  extract  once  daily  ; 
the  second  dose  produced  vomiting,  collapse,  a  marked  rise  of  temperature  and 
pulse.     Dose  reduced  to  two  drops. 

Immediate  result  of  the  treatment. — Complete  disappearance  of  the  myxcede- 
matous  symptoms,  followed  by  rapid  and  continuous  improvement. 

Subsequent  progress. — 2bth  May. — Hair  growing;  has  cut  one  tooth. 

3rd  July. — Has  six  teeth ;  the  umbilical  hernia  has  entirely  disappeared. 
Beginning  to  say  a  few  small  words. 

2,rd  November. — Thriving  splendidly  ;  has  fourteen  teeth  ;  looks  perfectly 
bright  and  intelligent  ;  talks  a  great  deal  in  a  language  peculiar  to  herself. 

wlh  May  1895. — Height  =  yj\  inches;  has  therefore  grown  11  inches  since 
the  treatment  was  commenced  two  years  ago,  and  3  inches  during  the  past 
year ;  weighs  36  lbs.  In  excellent  health  and  spirits  ;  legs  getting  stronger 
daily,  and  quite  straight ;  walks  fully  a  mile  every  day ;  very  musical ;  always 
good-tempered ;  very  slow  at  talking  ;  can  say  plenty  of  words,  but  does  not 
string  them  together.  Cheeks  rosy  ;  eyes  bright  ;  mouth  is  now  always  kept 
shut  ;  tongue  never  protrudes  ;  teeth  strong  ;  hair  long  and  thick  ;  skin  beauti- 
fully clear  and  soft  ;  cannot  yet  feed  herself,  unless  her  hand  is  guided  to  her 
mouth;  appetite  excellent;  bowels  quite  regular;  sleeps  splendidly. 

April  1898. — Continues  to  improve  ;  physically  strong  ;  has  lost  two  of  her 
first  teeth  ;  mentally  improved,  but  still  backward. 

The  height  at  different  dates  was  as  follows  : — 30th  March  1893  (before 
thyroid  treatment)  =  26^  in.  ;  18th  May  1893  =  29  in.  ;  23rd  Nov.  1893  =  31!  in.  ; 
2nd  April  1894  =  34^  in.  ;  nth  May  1895  =  37},  in. 

Recorded  in  full,  "  Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  217. 

CASE  XXXVIII. —  Typical  Sporadic  Cretinism;  Immediate  Improvement 
under  Small  Doses  of  Thyroid  Extract ;  Rapid  Disappearance  of  All  the 
.  1  lyxojdemalous  Symptoms. 

Female,  aged  4,  admitted  Edinburgh  Royal  Infirmary,  6th  June  1894. 

Duration. — 3^  years  ;  symptoms  first  noticed  when  7  months  old. 

Apparent  cause. — None  ;  birth  easy. 

Family  history. — Six  other  children  ;  three  alive  and  well  ;  three  dead  (one 


MYXGEDEMA.  377 

still-born,  one  died  immediately  after  birth,  one  at  age  of  9  weeks  from  gastro- 
intestinal catarrh).  No  evidence  of  inherited  syphilis.  Since  the  birth  of 
patient,  mother  has  had  occasional  epileptic  fits. 

Condition  on  admission. — Height  =  27  inches  ;  weight  =  1  st.  8  lbs.  ; 
slightly  anaemic  ;  face  ugly  ;  mouth  very  large  ;  lips  thick  and  of  a  bluish 
colour;  lower  lip  everted;  tongue  very  large  and  always  protruding;  eyelids 
markedly  swollen ;  a  slight  pink  blush  on  each  cheek  and  over  the  tip  of  the 
nose:  anterior  fontanelle  widely  open  ;  hair,  which  is  fair,  ragged  and  coarse, 
scanty  over  the  greater  part  of  the  head ;  more  plentiful  at  the  sides  over  the 
parietal  bones  than  over  the  occiput  or  vertex ;  scalp  encrusted ;  neck  short  and 
thick;  thyroid  cannot  be  felt;  elastic  swellings  above  the  clavicles;  thick  pad 
of  fat  at  the  root  of  the  neck  behind;  masses  of  fat  or  myxcedematous  swellings 
below  the  chin ;  abdomen  very  large ;  a  small  umbilical  hernia ;  pelvis  very 
narrow  in  proportion  to  the  abdomen ;  chest  walls  seem  to  be  infiltrated  with 
solid  oedema  ;  arms  short  and  broad ;  forearms  colossal ;  hands  large,  broad 
and  spade-shaped;  thenar  and  hypothenar  eminences  tense,  and  evidently 
distended  with  myxcedematous  swelling ;  hands  cold,  and  occasionally  cyanosed  ; 
skin  of  palms  wrinkled  and  dry;  legs  short  and  stout ;  calves  very  large,  hard 
and  swollen  ;  feet  always  cold  and  cyanosed;  skin  of  soles  wrinkled;  ends  of 
long  bones  thickened ;  no  beading  of  ribs  ;  spine  markedly  curved  ;  some  fatty 
or  myxcedematous  swelling  between  the  shoulders ;  a  growth  of  fine  hair  down 
the  back;  skin  dry;  no  moles,  warts,  or  nsevi.  Temperature  subnormal;  is 
always  worse  in  cold  weather  and  more  lively  in  warm  weather.  Cry  harsh  and 
low-toned — a  rough  grunt ;  takes  very  little  notice  of  anything  that  is  going  on 
around  her;  seems  pleased  with  toys;  can  say  "Ta-ta"  and  "Da-da";  is 
placid  in  disposition;  sleeps  a  great  deal.  Is  unable  to  creep,  stand,  or  walk. 
Well  nourished,  but  has  great  difficulty  in  swallowing ;  appetite  good ;  has  to 
be  fed  with  a  spoon ;  bowels  constipated ;  urine  free  from  albumen,  but  deposits 
mucus  ;  pulse  80.     Thyroid  cannot  be  felt. 

Thyroid  treatment  commenced  2nd  July  1894. 

Preparation  and  Dose. — f  gr.  solid  extract  daily,  subsequently  increased  to 
2j  grs.  daily. 

Immediate  result  of  treatment.  —  A  distinct  alteration  produced  by  two 
doses  (ih  grains  of  thyroid  extract) ;  rapid  disappearance  of  the  myxcedematous 
swelling,  rise  in  temperature,  pulse,  etc. 

On  t\th  July,  the  child  looked  distinctly  better;  eyes  more  widely  open  ; 
tongue  and  lips  slightly  less  swollen;  colour  better;  lips  less  blue;  the  swelling 
of  the  thenar  and  hypothenar  eminences  distinctly  less  marked ;  taking  its  food 
better.     No  change  in  temperature  and  pulse. 

Subsequent  progress. — On  1st  September  was  discharged,  very  much  im- 
proved in  every  way  ;  myxcedematous  swelling  gone  ;  much  more  intelligent  and 
lively;  anterior  fontanelle  closing;  umbilical  hernia  gone;  skin  soft;  the  dirty 
brown  crusts  had  almost  disappeared  from  the  scalp. 

11th  May  1895. — The  mother  says  she  has  been  very  well  since  her  dis- 
charge; is  a  fat,  plump  child;  skin  perfectly  smooth  and  soft;  sweats  naturally; 
head  covered  with  a  quantity  of  long,  soft,  perfectly  healthy  light  brown  hair ; 
anterior  fontanelle  closed ;  scalp  quite  clean ;  eight  teeth  which  she  cut  while  in 
the  Infirmary  under  thyroid  treatment  are  sound  and  good.  All  the  teeth  which 
were  cut  before  the  treatment  was  commenced  rotted  away  as  soon  as  they 
came  through  the  gum — a  striking  proof  of  the  improved  state  of  nutrition. 
Appetite  good  ;  the  bowels  still  somewhat  constipated  ;  can  stand  and  walk  a 


378  DISEASES   OF   THE    BLOOD   GLANDS. 

few  steps  with  the  help  of  a  hand,  but  not  by  herself ;  says  a  few  baby  words. 
Lips  still  thick,  mouth  still  large,  expression  still  suggestive  of  sporadic 
cretinism ;  only  grown  2  inches  in  the  past  nine  months,  whereas  in  the  two 
months  previously  (the  first  two  months  of  the  treatment)  she  grew  2-0-  inches. 
On  inquiry,  I  found  that  the  thyroid  had  not  been  given  regularly  ;  the  im- 
portance of  regular  administration  insisted  upon. 

The  height  at  different  dates  was  as  follows  : — 28th  June  1894  (before  thyroid 
treatment  commenced)  =  27  in.  ;  iSth  July  1894  =  27^  in. ;  30th  July  1894  =  28  in.  ; 
31st  August  1894  =  295  in.  ;   nth  May  1895  =  313-  in. 

Recorded  in  full,  "  Edinburgh  Hospital  Reports,"'  Vol.  iii.,  p.  224. 

CASE  XXXIX. — Comparatively  Mild  Case  of  Sporadic  Cretinism  ;  Marked 
Improvement  under  Thyroid  Treatment. 

Female,  aged  2fW,  seen  in  consultation  on  16th  August  1894. 

Duration. — Since  birth.  First  child;  labour  easy;  a  small  child;  at  birthr 
the  doctor  noticed  that  there  was  something  peculiar  about  it.  As  a  young 
infant  always  cold,  different  from  other  babies.     Has  not  grown  and  developed. 

Apparent  cause.  —  Congenital. 

Family  history. — Excellent ;  a  second  child,  also  a  girl,  born  a  week  ago, 
seems  quite  healthy,  but  has  a  small  umbilical  hernia. 

Present  condition. — A  big,  stout,  fat  child  ;  height  =  30  inches  ;  limbs 
sturdy-looking;  abdomen  relatively  large;  hands  small;  feet  of  good  size;  a 
small  umbilical  hernia  which  has  existed  since  birth.  Has  several  teeth  ;  all 
have  decayed  as  soon  as  they  came  through  the  gum.  Nose  squat ;  eyelids 
swollen;  skin  translucent  and  waxy-looking;  mouth  not  unduly  large;  tongue 
rather  large;  voice  rough  and  harsh.  Anterior  fontanelle  still  open;  head 
covered  with  a  good  deal  of  brown  hair  ;  slight  encrustation  of  scalp ;  skin 
dry  and  rough ;  absence  of  sweating.  Neither  the  nurse,  the  parents,  nor  the 
doctor  have  noticed  that  the  child  is  worse  in  cold  weather.  No  supraclavicular 
swellings.  Temperature  subnormal.  The  child  is  said  to  be  quite  intelligent, 
to  understand  what  is  said  to  it,  and  to  play  with  its  toys  ;  does  not  speak  ;  is- 
fond  of  animals;  good-tempered;  sleeps  well.  Appetite  very  small;  bowels 
obstinately  constipated  ;  urine  normal.     Thyroid  gland  cannot  be  felt. 

Thyroid  treatment  commenced  17th  August  1894. 

Preparation  and  Dose. — Dried  extract,  \\  grains  daily,  gradually  increased 
to  5  grains  daily. 

I  am  indebted  to  the  patient's  medical  attendant  for  the  following  notes  of 
the  progress  of  the  case. 

Immediate  result  of  the  treatment. — Slow  improvement  ;  rise  in  tempera- 
ture, etc. 

Subsequent  progress. — Marked  and  steady  improvement. 

jt/i  May  1895. — Looks  far  more  intelligent,  very  bright  and  happy,  and  the 
picture  of  robust  health.  Walks  with  almost  a  natural  step,  and  holds  herself 
beautifully  erect;  seems  to  take  an  interest  in  everything,  and  to  understand 
what  is  said  to  her,  but  cannot  talk  yet,  though  she  makes  various  attempts — 
inarticulate  sounds.  Is  still  taking  1  tabloid  (5  grs.)  daily.  Is  quite  a  different 
child  to  what  she  was  last  August,  and  would  apparently  be  perfect  if  she  could 
only  talk.  None  of  the  milk  teeth  which  have  been  cut  since  the  thyroid  treat- 
ment was  commenced  have  crumbled  or  decayed. 

28M  April  1898. — Since  last  note  has  made  steady  and  continuous  progress, 
and  is  now  not  very  different  from  any  ordinary  child  of  her  years.     Head  pro- 


MYXCEDEMA.  379 

portionately  a  little  large  ;  features  somewhat  plain  and  a  little  coarse  ;  voice 
still  husky  and  harsh,  but  can  talk  quite  distinctly,  intelligently,  and  nicely. 
Intelligence  quite  up  to  the  average  standard  of  a  child  of  her  age  (6).  Knows 
the  alphabet  ;  can  read  and  spell  words  of  three  or  four  letters.  Her  mother 
says  her  memory  is  not  very  good.  Is  fond  of  playing  and  amusements,  but 
does  not  perhaps  enter  into  them  with  the  same  eagerness  and  excitement  as 
her  younger  and  only  sister  does.  Has  grown  ten  inches  during  the  last  three 
years.  Is  strong  and  robust  and  enjoys  very  good  health.  Her  figure  is  per- 
fectly erect ;  limbs  straight  though  in  walking,  the  legs  are  kept  slightly  more 
apart  than  normal.  Most  of  the  milk  teeth  have  now  decayed ;  has  several 
teeth  of  the  permanent  set — all  the  incisors  and  several  molars ;  the  latter  are 
rather  large  teeth  and  not  very  evenly  set.  Constipation  occasionally  still 
troublesome. 

About  twelve  months  since,  the  parents  thought  they  would  like  to  try  the 
experiment  of  leaving  off  the  daily  dose  of  thyroid  extract  (five  grains).  At  the 
end  of  a  few  weeks,  the  mother  thought  the  legs  were  not  quite  so  straight ; 
this  observation  I  confirmed.  I  also  noticed  that  the  skin  was  markedly 
coarser  and  the  flesh  more  bulky.  I  advised  that  the  experiment  should  not  be 
continued  further,  but  that  the  daily  dose  of  thyroid  should  be  again  com- 
menced. 

The  height  at  successive  dates  was  as  follows  : — 16th  August  1894  =  30 
inches  ;  4th  October  1894  =  31^  inches  ;  7th  November  1894  =  32  inches  ; 
17th  December  1894  =  33^  inches  ;  19th  May  1895  =  365  inches  ;  21st  May 
1898  =  463-  inches. 

Recorded  in  full,  "Edinburgh  Hospital  Reports,"  Vol.  iii.,  p.  232. 

CASE  XL.  —  Typical  and  Very  Severe  Sporadic  Cretinism ;  the  Menstrual 
Function  Regularly  Performed ;  ATo  Thyroid  Treatment. 

Female,  aged  36,  seen  26th  January  1895. 

Duration. — From  birth  or  early  infancy. 

Apparent  cause. — None. 

Family  history. —  Mother  died  aged  31,  of  phthisis  ;  father  aged  54,  of 
gangrene  of  the  foot  following  rheumatism.  Six  children  in  the  family;  two 
sisters  aged  40  and  38,  alive  and  quite  normal  in  every  respect ;  a  brother  (a 
fine,  tall  man,  6  ft.  high)  died,  aged  28,  of  phthisis;  a  brother  and  sister  died 
a  few  months  after  birth — causes  of  death  unknown.  Six  step-brothers  and 
sisters,  all  well  developed  and  strong. 

Previous  history. — Birth  easy.  Several  attacks  of  bronchitis  in  infancy. 
Did  not  walk  till  three  years  old.  Has  hardly  grown  in  height  since  that  time, 
but  has  become  much  broader.  At  7,  abscess  in  leg;  at  16,  abscess  in  neck. 
Has  not  had  any  children's  diseases  ;  has  been  exposed  to  scarlet  fever. 

Present  condition. — Height  =  36  inches.  Body  very  broad  and  bulky. 
Back  markedly  curved  in  the  lumbar  region  ;  abdomen  large  and  prominent ; 
no  umbilical  hernia.  Face  full  and  swollen ;  eyelids  swollen  and  translucent ; 
no  pink  blush  on  the  cheeks ;  nose  squat  and  broad  (pug-shaped) ;  ears  rather 
large  ;  mouth  large,  lower  lip  pouting,  but  lips  not  much  swollen ;  tongue  large 
but  not  protruded  between  the  teeth;  palate  very  broad  and  flat ;  teeth  in  the 
upper  jaw  all  wanting.  Head  covered  with  a  profusion  of  very  coarse,  dark 
brown  hair.  Scalp  encrusted  till  the  age  of  25  ;  since  menstruation  has  become 
much  cleaner.  Anterior  fontanelle  closed;  it  was  very  late  in  closing.  Neck 
very  broad;  enormous  elastic  swellings    above   the   clavicles;    thyroid   gland 


380  DISEASES   OF   THE   BLOOD   GLANDS. 

cannot  be  felt  ;  some  fatty  or  myxedematous  swellings  in  the  anterior  fold  of 
the  axilla.  Forearms  colossal;  hands  enormously  broad  and  large;  fingers 
very  broad  and  flat ;  feet  very  broad  and  short ;  tibia?  somewhat  bent.  Com- 
plexion somewhat  earthy  coloured ;  skin  generally  dark,  dingy,  very  brown  in 
colour;  very  dry,  coarse  and  harsh.  Patient  never  sweats;  however  near  the 
fire  she  gets,  is  always  cold;  worse  in  cold  weather;  temperature  subnormal; 
hands  and  feet  often  blue  and  cold.  Is  of  a  cheerful  disposition;  fond  of  fun 
and  company.  Intellectual  development  is  that  of  a  child  of  five  or  six;  under- 
stands a  great  deal  that  is  said  to  her;  vocabulary  limited;  does  not  speak 
much.  Is  vain  and  fond  of  dress.  Sleeps  well.  Appetite  small;  does  not  like 
sweets;  bowels  quite  regular.     Urine  natural. 

The  nipples  and  areolae  are  somewhat  developed ;  fulness  in  the  position  of 
the  breasts  ;  no  pubic  hairs.  Since  the  age  of  25  has  menstruated  every  month  ; 
on  one  occasion,  a  year  and  a  half  ago,  the  discharge  stopped  for  three  months. 

The  exact  measurements  were  as  follows  : — 

Inches. 

Height  -------  36 

Circumference  round  abdomen  at  level  of  umbilicus  -  24 

,,  ,,       chest  at  level  of  nipples  -  -  22 

„  „       neck  over  thickest  part  of  glandular 

swellings      -  -  -  19 

,,  ,,       neck,  higher  up  -  14 

,,  .,       upper  arm  in  middle     -  -  6| 

,.  ,,       forearm,  thickest  part  -  7! 

„  „       hand      -  -  9l 

Length  of  hand  from  wrist  to  tip  of  middle  finger     -  4 

Circumference  of  foot,  thickest  part  8 

Length  of  foot  -  -  6 

Subsequent  progress. — Patient  remains  in  statu  quo.  The  relatives  refused 
to  allow  her  to  undergo  thyroid  treatment.  They  said  they  had  known  her  so 
long  in  her  present  condition  and  were  so  much  attached  to  her,  that  they  would 
not  like  to  have  her  changed,  even  for  the  better. 

Recorded  in  the  Lancet  10th  December  1898,  p.  1547. 


Additional    Note    on   the   Treatment   of  Myxcedema. — On 

page  324  I  have  inadvertently  omitted  to  state  that  Dr  Hovitz  of 
Copenhagen  was  the  first  to  introduce  the  method  of  thyroid 
feeding.  In  March  1892  he  successfully  treated  a  case  of 
myxcedema  by  the  administration  of  minced  raw  thyroid  in  the 
form  of  sandwiches. 


EXOPHTHALMIC    GOITRE. 

Definition  or  Short  Description. — Exophthalmic  goitre,  to 
which  the  synonyms  Graves'  disease  and  Basedozv's  disease  are  also 
applied,  is  a  very  interesting  affection.  In  typical  and  fully  de- 
veloped cases,  it  is  characterised  by: — (i)  increased  frequency  of  the 
heart's  action  and  palpitation  ;  (2)  enlargement  of  the  thyroid ;  (3) 
prominence  of  the  eyeballs  ;  (4)  general  nervousness  ;  (5)  a  fine 
muscular  tremor  ;  together  with,  in  many  cases,  (6)  a  number  of 
other  less  important  symptoms  which  will  be  afterwards  described 
in  detail. 

The  disease  is  much  more  common  in  women  than  in  men,  and 
is  usually  developed  in  young  women  (i.e.,  during  the  period  of 
active  sexual  life). 

There  is  still  much  difference  of  opinion  as  to  its  exact  patho- 
logy, though  of  recent  years  the  theory,  that  many  of  the  symptoms 
are  due  to  over-activity  or  perverted  activity  of  the  thyroid  gland, 
has  gradually  been  gaining  ground  and  may  now  be  accepted  as 
sufficiently  well  established.  This  statement  does  not,  however, 
imply  that  the  enlargement  of  the  thyroid  gland  is  the  primary  or 
initial  lesion  ;  it  is  more  probable,  I  think,  that  the  primary  cause 
of  the  disease  is  a  lesion,  or  rather  perhaps  a  functional  disturbance, 
of  some  part  of  the  nervous  system,  and  that  the  enlargement  of  the 
thyroid  gland  is  the  result  of  this  nervous  derangement. 

Historical  Note. — Although  cases  of  exophthalmic  goitre  had 
been  previously  described,  the  credit  of  recognising  the  connection 
between  the  accelerated  and  violent  action  of  the  heart  and  the 
enlargement  of  the  thyroid — two  of  the  great  cardinal  symptoms 
of  exophthalmic  goitre — undoubtedly  belongs  to  the  celebrated 
Dublin  physician  Graves  ;  hence  the  term  Graves'  disease.  In  a 
clinical  lecture  on  the  subject,  published  in  the  year  1835,  Graves 
pointed  out  that  the  disturbance  of  the  heart's  action  was  not 
(necessarily)  associated  with  organic  disease  of  the  heart.  Five 
years  later,  a  German  physician,  Basedow,  published  a  more  com- 
plete and  elaborate  account  of  the  clinical  features  ;  consequently 
in  Germany  the  disease  is  usually  termed  Basedow's  disease. 


;S2 


DISEASES   OF   THE    BLOOD   GLANDS. 


Etiology. 

Sex. — Exophthalmic  goitre  is  essentially  a  disease  of  the  female 
sex,  though  males  are  occasionally  affected.  It  is  probably  not  far 
from  the  truth  to  say  that  the  disease  is  nine  or  ten  times  more 
common  in  females  than  in  males.  In  my  series  of  79  cases,  73 
were  females  and  6  males.  (I  have  also  had  under  observation  two 
other  male  cases,  but  since  the  notes  have  been  mislaid  they  are  not 
included  in  the  series.  Consequently  in  81  cases  73  were  females 
and  8  were  males.) 

Age. — Exophthalmic  goitre  may  occur  at  any  age,  but  in  the 
great  majority  of  cases  the  disease  is  developed  during  active  sexual 
life.  If  I  may  judge  from  my  own  experience,  the  most  common 
period  for  its  commencement  is,  in  women,  between  the  ages  of  15 
and  35,  and,  in  men,  between  the  ages  of  30  and  45.  Though 
cases  have  been  observed  both  in  children  and  old  people,  all 
observers  are  agreed  that  the  disease  is  extremely  rare  before  the 
age  of  12  and,  comparatively  speaking,  very  rarely  developed  after 
the  age  of  50.  Divel  has  reported  a  case  in  a  child  aged  2-J-  years, 
and  Charcot  a  case  at  the  age  of  68. 

In  my  series  of  79  (male  and  female)  cases,  the  average  age  of 
the  patients  when  they  came  under  my  notice  was  34  years  ;  the 
average  age  of  the  females  was  33  and  of  the  males  41  years. 

The  average  age  of  onset  in  76  (male  and  female)  cases  was  31 
years  ;  the  average  age  of  onset  in  70  female  cases  was  30  years, 
and  in  6  male  cases  36  years. 

The  age  at  onset  in  the  76  cases  (male  and  female)  in  which  the 
date  of  commencement  was  ascertained,  is  shown  in  the  following 
table. 

Table  10,  showing  the  Age  at  the  Onset  in  seventy-six 
cases  of  Exophthalmic  Goitre. 


Below  1 

2  years 

- 

- 

= 

0  cases 

Between 

12  and 

14  years  inc 

usive 

= 

2 

3) 

14  and 

19 

>) 

, 

= 

10 

>J 

19  and 

24 

>) 

, 

= 

13 

)> 

24  and 

29 

>> 

, 

= 

1 1      , 

„ 

29  and 

34 

>) 

. 

= 

14      , 

n 

34  and 

39 

)» 

> 

= 

9      , 

)> 

39  and 

44 

>) 

> 

= 

9      , 

„ 

44  and 

49 

D 

, 

= 

3      , 

>> 

49  and 

54 

>> 

- 

= 

9 

j      1 

>) 

54  and 

59 

)> 

, 

= 

2 

Total 


=    76 


EXOPHTHALMIC   GOITRE.  383 

In  the  76  cases  in  which  the  age  at  onset  was  ascertained,  the 
disease  developed  in  69  cases  (or  90.7  °/o)  between  the  ages  of  15 
and  49.  In  two  cases  (or  2.6  °/0)  the  disease  developed  before  the 
age  of  15,  viz.,  at  12  and  14  years  of  age  respectively;  and  in  5 
cases  (or  6.6  °/0)  after  the  age  of  49,  viz.,  at  the  age  of  50  in  two 
cases,  at  51  in  one  case,  at  55  in  one  case,  and  at  56  in  one  case. 

Influence  of  Marriage  and  Child-bearing. — In  the  73  female 
cases  included  in  my  series  of  79  cases,  47  were  single  women,  and 
26  were  married  women  or  widows.  In  the  26  cases  in  which  the 
patients  were  married  or  widows,  the  disease  commenced  in  2  cases 
before  the  patients  were  married  ;  consequently  in  the  73  female 
cases,  the  disease  developed  in  single  women  in  49  cases  (or  67.1  °/J, 
and  in  married  women  in  24  cases  (or  32.8  °/0).  In  my  series,  there- 
fore, the  disease  was  twice  as  common  in  single  as  in  married  women. 

In  25  out  of  the  26  cases  in  which  the  patients  were  married 
women  and  in  which  the  number  of  pregnancies  was  noted,  the 
average  number  of  pregnancies  was  3.2.  In  the  two  cases  in  which 
the  disease  was  already  in  existence  before  the  patients  married, 
marriage  seemed  in  one  case  (Case  XVI.)  to  be  followed  by  perma- 
nent, and  in  one  case  (Case  XXII.)  by  temporary,  benefit;  in  the 
latter  case,  a  relapse  occurred  immediately  after  the  birth  of  the 
first  child  ;  in  another  case  (Case  L.),  the  disease  developed  imme- 
diately after  pregnancy. 

Mode  of  Onset ;  Exciting  and  Predisposing  Causes. — In 
some  cases  the  symptoms  develop  insidiously  and  without  any 
obvious  cause;  but  in  others  the  onset  is  more  acute.  In  many 
cases,  the  exciting  cause  appears  to  be  a  fright,  profound  emotional 
disturbance  or  mental  shock,  over-fatigue,  etc. ;  and  in  connection 
with  the  influence  of  fright  and  mental  shock  it  is  interesting  to 
note,  as  Dr  Hector  Mackenzie  has  pointed  out,  that  the  physical 
effects  of  sudden  fright  and  terror  closely  resemble  the  symptoms 
and  appearances  characteristic  of  exophthalmic  goitre.  Thus  he 
states  : — "  The  descriptions  given  by  Darwin  and  Sir  Charles  Bell 
of  the  condition  presented  by  persons  under  the  influence  of  intense 
fear  at  once  suggest  the  symptoms  of  exophthalmic  goitre.  The 
heart  beats  quickly  and  violently,  so  that  it  palpitates  or  knocks 
against  the  ribs.  There  is  trembling  of  all  the  muscles  of  the  body. 
The  eyes  start  forward  and  the  uncovered  and  protruding  eyeballs 
are  fixed  on  the  object  of  terror  ;  the  skin  breaks  out  into  a  cold 
and  clammy  sweat,  and  the  face  and  neck  are  flushed  or  pallid. 
The  intestines  are  affected."  * 


*  Clifford  Allbutt's  "  System  of  Medicine,"  Vol.  iv.,  p.  490. 


384  DISEASES   OF   THE   BLOOD   GLANDS. 

Occasionally  the  exhaustion  produced  by  an  acute  illness,  espe- 
cially influenza,  or  a  loss  of  blood  seems  to  be  the  exciting  cause. 
In  exceptional  cases,  the  disease  has  developed  after  a  head  injury. 
Anything  which  lowers  the  nerve  tone  and  produces  exhaustion 
and  debility  may  probably  act  as  an  exciting  cause  in  persons  who 
are  predisposed  to  the  disease.  Peripheral  irritation  originating  in 
the  nose  or  in  the  abdominal  or  pelvic  viscera  seems  in  some  cases 
to  be  the  exciting  cause.  Some  of  the  patients  affected  with  ex- 
ophthalmic goitre  are  anaemic,  and  almost  all  observers  are  agreed 
that  anaemia  is  apt  to  play  a  part  in  the  production  of  the  disease. 

Gautier  has  suggested  that  cases  of  exophthalmic  goitre  should 
be  divided  into  two  great  groups,  viz.,  (1)  Cases  of  primary  exoph- 
thalmic goitre  (these  he  regards  as  due  to  a  functional  disturbance 
of  the  nerve  centres) ;  and  (2)  Cases  of  secondary  or  symptomatic 
exophthalmic  goitre  (these  he  thinks  are  the  result  of  some  obvious 
peripheral  lesion) ;  but  I  doubt  whether  it  is  possible  to  draw  a 
sharp  line  of  distinction  between  these  so-called  primary  and 
secondary  forms  of  the  disease,  though  the  fact  that  in  some  cases 
the  disease  appears  to  have  its  exciting  cause  in  some  form  of 
peripheral  irritation  should  be  kept  in  view  for  the  purposes  of 
treatment. 

It  may,  I  think,  be  doubted  whether  some  of  the  conditions 
which  have  just  been  enumerated  were  the  actual  primary  cause 
of  the  disease.  It  is  probable  that,  in  some  cases  at  all  events, 
in  which  a  fright,  emotional  disturbance,  or  peripheral  irritation 
appears  to  be  the  cause  of  exophthalmic  goitre,  the  disease  was 
already  present  in  a  slight  and  modified  form,  and  that  the 
emotional  disturbance  merely  aggravated  the  symptoms  and 
brought  them  into  prominence,  perhaps  by  deranging  the  tissue 
metabolism  or  upsetting  the  nervous  balance. 

In  78  of  my  series  of  79  cases,  the  presence  or  absence  of  a 
cause  for  the  disease  was  noted.  In  45  of  these  78  cases,  there  was 
no  apparent  cause  ;  in  1 5  cases,  the  disease  developed  immediately 
after,  and  apparently  as  the  result  of,  a  nervous  shock,  profound 
mental  anxiety,  etc.  ;  in  7  cases,  after  an  attack  of  influenza ;  in  2 
cases,  after  loss  of  blood  ;  in  2  cases,  immediately  after  childbirth  ; 
and  in  1  case  the  following  causes  respectively  were  blamed,  viz. : — 
sleeping  in  a  damp  bed,  the  occurrence  of  the  menopause,  an  attack 
of  rheumatic  endocarditis,  over-exertion  shooting,  an  attack  of 
bronchitis,  privation  and  starvation.  In  1  case,  the  patient,  aged  27 
when  the  symptoms  of  exophthalmic  goitre  developed,  had  had  an 
enlarged  thyroid  (without  any  other  symptoms)  since  she  was  9 
years  old. 


EXOPHTHALMIC   GOITRE.  385 

Hereditary  and  Family  Influences. — Many  of  the  subjects  of 
exophthalmic  goitre  inherit  a  tendency  to  nerve  disease.  In  rare 
cases,  the  disease  appears  to  be  directly  handed  down  from  parent 
to  child  ;  but  direct  inheritance  (mother  and  daughter  both  affected) 
is  extremely  rare.  Cases  are  not  very  uncommon  in  which  more 
than  one  member  of  the  same  family  is  affected.  In  the  great 
majority  of  cases  in  which  a  patient  who  is  affected  with  exoph- 
thalmic goitre  inherits  a  tendency  to  nerve  disease,  the  parents  or 
near  relatives  have  been  affected  with  some  other  form  of  nervous 
malady,  such  as  general  nervousness,  hysteria,  epilepsy,  or  insanity. 

In  my  series  of  79  cases,  a  hereditary  or  family  tendency  to  the 
disease  was  noted  in  5  instances.  In  one  case  (Case  XXL),  a  sister 
had  a  large  goitre;  in  one  case  (Case  XLVIII.),  an  aunt  suffered 
from  exophthalmic  goitre  ;  in  one  case  (Case  LXXVIII.),  a  cousin 
had  exophthalmic  goitre  ;  in  Cases  LXXIII.  and  LXXIV.,  the 
patients  were  sisters  ;  in  Case  L.,  the  patient's  sister  also  suffered 
from  exophthalmic  goitre,  and  it  is  interesting  to  note  that  in 
both  of  these  cases  the  disease  developed  after  pregnancy  and 
that  in  both  cases  the  patients  suffered  during  pregnancy  from 
albuminuria. 

In  a  considerable  number  of  my  cases,  the  patients  came  of 
markedly  neurotic  families,  and  in  several  instances  were,  prior  to 
the  commencement  of  the  disease,  themselves  markedly  neurotic. 
In  a  few  instances,  they  were  the  subjects  of  other  forms  of  nervous 
disease ;  one  patient,  for  example,  suffered  from  epilepsy,  another 
from  asthma,  a  third  from  diabetes,  etc.  In  several  of  my  cases, 
there  was  a  marked  hereditary  history  of  tubercle  (phthisis,  etc.), 
but  I  doubt  whether  this  tendency  was  greater  than  it  would  have 
been  in  any  other  series  of  79  cases  of  medical  disease. 

Clinical  History. 

Until  comparatively  recently,  three  symptoms — viz.,  (1)  In- 
creased frequency  of  the  heart's  action  ;  (2)  Enlargement  of  the 
thyroid  ;  and  (3)  Prominence  of  the  eyeballs — were  considered  to 
be  the  cardinal  or  fundamental  symptoms  of  the  disease  ;  but  of 
recent  years  it  has  been  generally  recognised  that  in  typical  and 
fully  developed  cases  other  symptoms  are  also  present.  In  a  very 
large  proportion  of  cases,  a  peculiar  form  of  tremor,  the  special 
features  of  which  I  shall  presently  describe  in  detail,  occurs  ;  this 
tremor  is  so  constant  that  Charcot  considered  it  to  be  one  of  the 
primary  or  fundamental  symptoms.  Another  symptom,  which  is 
so  constant  and  characteristic  that  it  must  undoubtedly  be  con- 
sidered to  be  a  primary  or  fundamental  symptom,  is  nervous  irrita- 

2  B 


:S6 


DISEASES   OF   THE   BLOOD   GLANDS. 


bility  and  instability — a  condition  of  general  nervousness,  as  it  may 
be  termed. 

In  the  following  table,  which  is  modified  from  Charcot,  the 
symptoms  of  exophthalmic  goitre  are  enumerated  and  classified. 
It  is  almost  unnecessary  to  say  that  all  of  the  symptoms  enume- 
rated in  the  table  are  rarely  present  in  the  same  case. 

Table  ii,  showing  the  Symptoms  which  may  be  present 
in  cases  of  Exophthalmic  Goitre. 

I  Increased  frequency  of  heart's  action,  palpitation,  throbbing  of 
Primary  the  veSsels,  etc. 

J  Enlargement  of  the  thyroid. 

I"1  Prominence  of  the  eyeballs. 
General  nervousness. 
Fine  rhythmical  vibratory  tremor. 
Diarrhoea. 
Vomiting. 

Loss  of  appetite  ;  Bulimia  ;  Sudden  fits  of  hunger. 
Thirst. 
Jaundice. 


OR 


Cardinal 


Digestive 
organs. 


(Co 
line 


'ough. 
Respiratory  J  increased  frequency  of  respiration. 

'  niminished  inspiratory  expansion  (Bryson's  symp- 
tom). 


Nervous 
system. 


Secondary1 


hitegumen- 
tary  system. 


Von  Graefe's  symptom. 

Stellwag's  symptom  ;  Absence  of  reflex  blinking. 
Defective  convergence  (Mobius). 
Ophthalmoplegia  externa. 
Paralysis  ;  Peculiar  form  of  paraplegia. 
Epileptiform  convulsions  ;  Chorea. 
Headache  ;  Neuralgia  ;  Angina  pectoris. 
Psychical  modifications  (mental  depression,  mania- 
cal excitement,  etc.). 

Sweatings  ;  Flushings  ;  Sensations  of  heat ;  Rises 

of  temperature. 
Diminished  electrical  resistance. 
Increased  pigmentation. 
Leucoderma  ;  Other  skin  eruptions. 
Loss  of  hair  ;  Atrophy  of  nails. 


/  Polyuria. 
Urinary     J  Albuminuria. 
system.       [  Glycosuria. 

Generative   /"Menstrual  derangements. 
system.       [  Loss  of  sexual  desire  ;  Impotence. 

General      (Debility;    Loss   of  weight;   Anaemia;    Cachexia 
\  (         (Edema  of  the  lower  extremities. 


EXOPHTHALMIC   GOITRE.  387 

The    Primary   Symptoms    of    Exophthalmic   Goitre. — The 

great  primary,  fundamental  symptoms  of  exophthalmic  goitre  are, 
then,  (1)  Increased  frequency  of  the  heart's  action  ;  (2)  Enlarge- 
ment of  the  thyroid  ;  (3)  Prominence  of  the  eyeballs  ;  (4)  A  con- 
dition of  general  nervousness  ;  and  (5)  Fine  rhythmical  tremor. 

The  appearance  which  a  patient  who  is  affected  with  exoph- 
thalmic goitre,  in  its  typical,  classical  and  fully  developed  form, 
presents,  is  highly  characteristic.  Graves'  disease  is,  in  fact,  one  of 
the  few  diseases  which  can,  usually,  be  recognised  at  a  glance.  In 
typical  and  fully  developed  cases,  the  physiognomy  of  the  patient 
is  pathognomonic.  The  remarkable  prominence  of  the  eyeballs 
and  the  startled,  staring,  and  in  some  cases  almost  savage  appear- 
ance of  the  face,  are  very  peculiar.  These  features  and  the  obvious 
enlargement  of  the  thyroid  gland  are  admirably  represented  in  my 
Atlas  of  Clinical  Medicine,  Plates  XLIX.  and  L. 

It  must  not,  however,  be  supposed  that  one  can  recognise  all 
cases  of  exophthalmic  goitre  at  the  first  glance.  In  some  cases, 
there  is  no  prominence  of  the  eyeballs ;  in  others,  there  is  no 
perceptible  enlargement  of  the  thyroid  ;  while,  in  others  again, 
there  is  neither  prominence  of  the  eyeballs  nor  enlargement  of  the 
thyroid.  The  symptoms  which  in  my  experience  are  constant  are 
■debility,  general  nervousness,  and  increased  frequency  and  irrita- 
bility of  the  heart's  action.  Without  these  symptoms  a  diagnosis 
•of  Graves'  disease  is,  so  far  as  we  at  present  know,  never  justifiable. 
The  fine  muscular  tremor  and  increased  secretion  of  sweat  are  also 
very  frequent  and  constant  symptoms.  Cases  in  which  the  disease 
is  developed  in  a  fragmentary  or  imperfect  manner  are,  if  I  may 
judge  from  my  own  experience,  somewhat  more  common  in  men 
than  in  women.  It  would  appear  that  males  are  not  only  less 
frequently  affected  with  exophthalmic  goitre  than  females,  but  that, 
when  the  disease  does  develop  in  the  male,  its  clinical  features  are 
apt  to  be  less  perfect  and  complete.  It  must  not,  however,  be 
supposed  that  the  disease  is  less  severe  or  less  serious  in  men  than 
in  women,  for  this  is  by  no  means  the  fact. 

Several  well  marked  but  atypical  or  rudimentary  cases  of 
exophthalmic  goitre  in  males  have  come  under  my  observation. 
The  first  case  of  the  kind  which  I  clearly  recognised — only,  how- 
ever, after  its  true  nature  had  been  pointed  out  by  Sir  William 
Jenner — was  that  of  a  gentleman  whom  I  saw  in  consultation  with 
my  friend  Dr  Croom  many  years  ago.  He  was  a  dark-skinned, 
very  nervous  man,  some  45  or  50  years  of  age ;  his  pulse  was 
habitually  very  frequent,  and  the  characteristic  nervousness  and 
tremor  were  well  marked  ;  but  the  eyeballs  were  not  prominent, 


388  DISEASES   OF   THE   BLOOD   GLANDS. 

and  the  thyroid  was  not  enlarged.  Another  case,  in  which  the 
symptoms  were  almost  identical  with  those  of  the  case  to  which  I 
have  just  referred,  was  that  of  a  clergyman,  under  the  care  of  Dr 
Millard  ;  he  had  been  seen  some  time  previously  by  Professor 
Charcot,  who  had  given  a  written  diagnosis  of  Graves'  disease.* 

In  my  series  of  79  cases  of  exophthalmic  goitre,  enlargement  of 
the  thyroid  was  absent  in  5  cases  ;  prominence  of  the  eyeballs  was 
absent  in  14  cases ;  and  both  enlargement  of  the  thyroid  and 
prominence  of  the  eyeballs  were  absent  in  5  cases. 

Let  us  now  consider  the  more  important  symptoms  in  detail. 

Increased  Frequency  of  the  Heart's  Action  and  Disturbance 
of  the  Circulation. — In  many  cases,  these  are  the  first  symptoms 
which  are  complained  of.  In  fully  developed  cases,  the  pulse  usually 
numbers  120,  130,  or  150  in  the  minute  ;  in  some  cases  indeed,  it  is 
more  frequent — 180,  200,  or  even  more  in  the  minute.  In  the 
slighter  forms  of  the  disease  and  in  those  cases  in  which  the 
symptoms  are  subsiding,  the  pulse  may  number  only  100  or  90  in 
the  minute.  It  is  important  to  note  that  slowing  of  the  pulse  is 
perhaps  the  most  certain  sign  of  improvement  which  we  possess  ; 
vice  versa,  a  very  quick  pulse  or  increasing  rapidity  of  the  pulse, 
are  unfavourable  indications.  The  behaviour  of  the  pulse  under 
treatment  is  a  most  important  guide  for  prognosis.  The  nervous 
equilibrium  of  patients  affected  with  Graves'  disease  is  so  unstable 
that  the  slightest  emotional  disturbance  or  excitement,  such,  for 
example,  as  that  occasioned  by  the  presence  of  the  doctor,  is  apt  to 
produce  an  attack  of  palpitation  and  to  cause  a  marked  increase  in 
the  frequency  of  the  pulse.  In  trying  to  form  an  estimate  of  the 
severity  of  any  given  case  from  the  condition  of  the  pulse,  this 
must,  of  course,  be  allowed  for.  The  extreme  irritability  of  the 
heart  is,  indeed,  one  of  the  most  striking  features  of  the  disease. 
In  exophthalmic  goitre,  the  heart  seems  to  run  loose  ;  it  would 
appear  that  its  action  is  no  longer  restrained  or  reined  in  by  the 
inhibitory  influence  of  the  vagus  ;  the  accelerating  influence  of  the 
sympathetic  seems  to  have  the  upper  hand,  and  irritations  and 
stimuli,  emotional  or  other,  which  produce  little  or  no  effect  upon  a 
normal  heart,  may  lash  it,  as  it  were,  into  an  altogether  unnatural 
and  furious  activity. 

In  rare  cases,  the  increased  frequency  of  the  cardiac  action 
appears  to  be  paroxysmal  and  intermittent.  In  cases  of  this  kind, 
more  especially  if  the  thyroid  was  not  enlarged  and  the  eyeballs 
were  not  prominent,  the  diagnosis  would  be  most  difficult.     If  the 

*  These  two  cases  are  not  included  in  the  series  of  79  cases  (see  Table  12). 


EXOPHTHALMIC   GOITRE.  389 

physician  should  happen  to  see  such  a  case  during  an  a-frequent 
interval  (i.e.,  at  a  time  when  the  paroxysm  of  accelerated  action 
was  not  present),  a  positive  diagnosis  could  not  (in  the  absence  of 
exophthalmos  and  thyroid  enlargement)  be  made.  Such  a  difficulty 
in  diagnosis  is  not,  however,  likely  to  occur.  It  is,  I  fancy, 
more  theoretical  than  real.  In  the  vast  majority  of  cases  of  ex- 
ophthalmic goitre,  the  agitation  and  nervous  excitement,  which  the 
patient  feels  under  the  examination  of  the  physician,  would,  even  if 
the  pulse  were  at  times  slow,  set  the  heart  off  at  a  gallop  and  excite 
a  paroxysm  of  increased  frequency. 

In  my  series  of  79  cases,  the  pulse  frequency  was  noted  in  74 
cases.  The  average  frequency  in  these  74  cases  was  129  per 
minute ;  but  it  should  be  stated  that  this  probably  represents  a 
higher  frequency  of  pulse  than  was  actually  present,  for  many  of 
the  cases  were  only  seen  once  in  consultation  and  the  pulse  was 
consequently  in  many  of  these  cases  temporarily  increased  by 
nervous  excitement.  I  have,  however,  endeavoured  to  eliminate 
this  error  so  far  as  possible,  by  counting  the  pulse  at  the  end  as 
well  as  at  the  beginning  of  the  visit.  The  lowest  pulse  frequency 
which  was  noted  in  these  74  cases  was  86  and  the  highest  240. 

Many  patients  affected  with  exophthalmic  goitre  complain  of  a 
feeling  of  throbbing  or  pulsation  in  the  vessels  of  the  head  and  neck, 
and  in  some  cases  in  the  vessels  of  the  whole  body  ;  but  they  do 
not,  as  a  rule,  appear  to  suffer  in  the  same  degree  and  to  feel  the 
same  sensations  of  anxiety  and  dread  as  patients  often  do  who 
are  suddenly  seized  with  a  severe  attack  of  ordinary  functional  pal- 
pitation. I  have  emphasised  the  word  suddenly,  for  the  sudden, 
intermittent,  and  unaccustomed  character  of  an  ordinary  attack  of 
palpitation  seems  to  me  to  be  a  sufficient  explanation  of  the  very 
different  character  of  the  subjective  sensations  which  the  patient 
experiences  in  the  two  cases.  There  can  be  little  doubt  that,  if  the 
heart  of  a  healthy  individual  were  suddenly  made  to  beat  in  the 
way  in  which  the  heart  of  a  patient  affected  with  severe  Graves' 
disease  beats,  the  healthy  individual  would  experience  all  the 
alarming  symptoms  which  are  apt  to  be  associated  with  an  ordinary 
attack  of  functional  palpitation.  In  exophthalmic  goitre,  the  irri- 
tability of  the  heart  continues  for  months  or  years  ;  it  becomes,  as 
it  were,  part  and  parcel  of  the  individual.  It  is  natural,  therefore, 
to  suppose  that,  when  a  heart  whose  action  is  habitually  increased 
and  unduly  irritable  becomes  temporarily  still  more  accelerated — 
accelerated  to  a  degree  which,  in  a  normal  individual,  is  usually 
attended  with  the  alarming  sensations  of  a  violent  attack  of  palpita- 
tion— the  discomfort  would  be,  comparatively  speaking,  slight. 


390  DISEASES   OF   THE   BLOOD   GLANDS. 

In  my  series  of  79  cases,  palpitation  was  present  in  yj  cases, 
absent  in  1  case  and  not  noted  in  1  case.  Throbbing  of  the  vessels 
of  the  neck  was  present  in  58  cases,  absent  in  10  cases,  and  not 
noted  in  1 1  cases. 

In  exophthalmic  goitre,  the  pulse  is  usually  small  in  size  and 
regular  in  rhythm.  In  some  cases,  it  is  more  or  less  dicrotic.  In 
the  later  stages  of  the  disease,  the  pulse  may  become  irregular  or 
intermittent,  as  the  result  of  cardiac  failure,  dilatation,  or  organic 
valvular  disease ;  but  it  is  important  to  remember  that  in  the 
majority  of  cases  of  exophthalmic  goitre  there  is  no  organic 
valvular  lesion. 

In  some  cases,  the  heart  is  found  after  death  to  be  little,  if  at 
all,  larger  than  normal  ;  but  in  other  cases,  and  I  am  disposed  to 
think  that  they  comprise  the  great  majority  of  severe  and  long- 
continued  cases,  the  heart  becomes  dilated  or  (but  this  is,  I  think, 
less  frequent)  to  some  extent  hypertrophied.  In  a  large  proportion 
of  the  severe  cases  which  have  come  under  my  own  observation, 
the  heart  was  more  or  less  enlarged  ;  and  in  some  of  them  there 
was  distinct  evidence  of  mitral  or  (but  this  was  less  frequent)  of 
tricuspid  regurgitation. 

Towards  the  termination  of  the  case  oedema  of  the  feet  is  not 
unfrequently  developed.  In  my  series  of  79  cases,  oedema  of  the 
feet  was  present  in  13  cases,  absent  in  56  cases,  and  not  noted  in 
1 1  cases. 

In  most  well  marked  cases  of  exophthalmic  goitre,  some 
shortness  of  breath  on  exertion,  which  is,  in  part  at  least,  of  cardiac 
origin,  is  complained  of.  In  my  series  of  79  cases,  shortness  of 
breath  was  complained  of  in  39  cases,  was  said  to  be  absent  in  20 
cases,  and  was  not  noted  in  20  cases. 

On  physical  examination,  the  area  of  visible  impulse  is  usually 
increased,  and  in  many  cases  an  abnormal  degree  of  epigastric 
pulsation  is  present.  The  action  of  the  heart  is  usually  sharp  and 
flapping  in  character.  The  first  sound  is  usually  short  in  duration 
and  accentuated  in  tone ;  in  rare  cases,  the  heart  sounds  are  so 
loud  as  to  be  auto-audible.  A  systolic  murmur  can  frequently 
be  heard  in  the  mitral  or  pulmonary  areas,  and  in  some  cases  in 
the  tricuspid  or  aortic  areas.  In  some  cases,  these  murmurs  are 
no  doubt  haemic  in  character  ;  in  others,  they  seem  to  be  inde- 
pendent of  an;umia,  and  perhaps  due  to  the  altered  character  of 
the  cardiac  contractions.  Systolic  murmurs  in  the  mitral  and 
tricuspid  areas  are  probably,  in  many  cases,  the  result  of  dilatation 
of  the  ventricles.  In  exceptional  cases,  organic  lesions,  the  result 
of  endocarditis,  arc  present;  but,  in  my  experience,  the  subjects  of 


EXOPHTHALMIC   GOITRE.  391 

Graves'  disease    comparatively  rarely  suffer    from    acute  articular 
rheumatism  or  endocarditis. 

In  my  series  of  79  cases,  the  presence  or  absence  of  enlargement 
of  the  Jieart  was  noted  in  71  cases  ;  in  21  cases  the  heart  was  more 
or  less  enlarged,  and  in  the  remaining  50  cases  it  was  not  (so  far  as 
could  be  judged  from  clinical  examination)  enlarged. 

In  the  79  cases,  valvular  murmurs  were  present  in  23  cases, 
absent  in  49  cases,  and  not  noted  in  7  cases.  In  the  23  cases  in 
which  valvular  murmurs  were  present,  the  murmur  was  a  systolic 
mitral  murmur  in  1 1  cases,  a  pulmonary  systolic  murmur  in  4  cases, 
a  mitral  and  pulmonary  systolic  murmur  in  3  cases,  a  mitral  pre- 
systolic murmur  in  2  cases,  a  mitral  and  tricuspid  systolic  murmur 
in  1  case,  and  a  systolic  murmur  audible  in  all  the  valvular  areas 
in  2  cases. 

Exaggerated  pulsation  in  the  vessels  of  the  neck  is  in  many  cases 
a  striking  symptom  ;  the  pulsation  may  be  hammering  in  character. 
Pulsations  and  thrills  can,  in  a  certain  proportion  of  cases,  be  felt 
over  the  enlarged  thyroid.  Inordinate  pulsation  (palpitation)  of  the 
abdominal  aorta  is  frequent.  In  some  cases  the  patients  complain 
of  excessive  pulsations  all  through  the  body.  The  veins  of  the  neck 
are,  in  some  cases,  unduly  prominent,  and,  in  the  advanced  stages 
of  the  disease,  true  venous  pulsation  in  the  neck  is  occasionally 
present.  Blowing  systolic  murmurs  can  often  be  heard  in  the 
carotids,  over  the  enlarged  thyroid,  and  sometimes  over  the  enlarged 
eyeballs.  In  many  cases,  a  loud  venous  hum  is  audible  at  the  root 
of  the  neck.  Tinnitus,  headache  and,  less  frequently,  vertigo, 
which  are  not  uncommon,  are  probably  in  many  cases  due  to  these 
derangements  of  the  circulatory  system. 

The  exact  cause  of  the  increased  frequency  of  the  heart's  action 
is  a  matter  of  dispute.  According  to  one  view,  it  is  the  result  of 
overaction  (irritation)  of  the  sympathetic  ;  according  to  another,  of 
diminished  action  (paralysis)  of  the  vagus  ;  perhaps  both  views  are 
correct. 

Enlargement  of  the  thyroid. — In  typical  and  fully  developed 
cases,  this  is  a  striking  feature.  The  enlargement  of  the  thyroid 
may  be  developed  before,  simultaneously  with,  or  after  the  increased 
frequency  of  the  heart's  action  and  the  exophthalmos,  though  it  is 
sometimes  the  first  symptom  which  attracts  the  attention  of  the 
patient ;  in  other  cases,  the  patient  is  not  aware  of  the  alteration 
until  her  attention  is  directed  to  it  by  the  physician.  In  some 
cases,  as  I  have  already  more  than  once  stated,  the  thyroid  does 
not  appear  to  be  enlarged  ;  but  in  this  connection  it  must  be  re- 
membered that  slight  enlargement  of  the  thyroid  gland  is  difficult 


392  DISEASES   OF   THE   BLOOD   GLANDS. 

to  detect  and  may  easily  escape  notice.  In  some  of  the  cases  in 
which  the  thyroid  is  not  obviously  enlarged,  exophthalmos  is  also 
wanting. 

The  enlargement  of  the  thyroid  is  usually  moderate  in  degree ; 
the  gland  rarely  attains  to  such  a  large  size  as  in  ordinary  goitre. 
The  enlarged  gland  usually  feels  elastic  and  in  some  cases  soft,  but 
in  others  it  is  hard  and  even  nodulated.  Dilated  veins  may  some- 
times be  seen  coursing  over  the  enlarged  thyroid  ;  and  pulsations 
and  thrills  can  often  be  felt  and  blowing  murmurs  heard  over  the 
enlarged  gland.  It  used  to  be  supposed  that  the  enlargement  of 
the  gland  was  chiefly  due  to  the  dilatation  of  the  thyroidal  vessels, 
but  the  correctness  of  this  opinion  is  very  questionable.  In  many 
cases  at  all  events,  the  gland  is  not  nearly  so  vascular  as  is 
commonly  supposed.  Nevertheless,  I  am  quite  satisfied  that  in 
some  cases  the  thrills  and  murmurs  are  actually  produced  in  the 
thyroid  itself,  and  are  not  merely,  as  has  been  suggested,  in  the 
adjacent  vessels. 

In  the  later  stages  of  exophthalmic  goitre,  the  enlarged  thyroid 
not  unfrequently  becomes  firmer  and  harder  than  it  was  in  the 
earlier  stages  of  the  case  ;  this  is  doubtless  due  to  the  development 
of  hyperplastic  and  sclerotic  changes  ;  and  it  is  very  interesting  to 
note  that  in  some  rare  cases,  in  which  these  sclerotic  and  inter- 
stitial changes  are  well  advanced,  and  in  which  the  glandular  tissue 
has  presumably  become  atrophied  and  destroyed,  the  symptoms  of 
exophthalmic  goitre  may  disappear  and  be  replaced  by  the  char- 
acteristic symptoms  of  myxcedema.  One  case  of  this  kind  has  come 
under  my  own  notice  (see  Case  XVII.,  p.  354).  As  I  have  already 
pointed  out,  many  of  the  symptoms  of  exophthalmic  goitre  are  the 
direct  opposite  of  those  which  characterise  myxcedema. 

All  parts  of  the  gland  are  usually  enlarged,  but  the  enlargement 
is  not  unfrequently  more  marked  on  one  side  than  the  other.  The 
right  lobe,  which  is  normally,  it  is  said,  slightly  larger  than  the  left, 
is,  as  a  rule,  more  enlarged  than  the  left. 

In  rare  cases,  the  enlargement  of  the  thyroid  and  the  exoph- 
thalmos are  unilateral ;  in  cases  of  this  description,  the  enlargement 
of  the  thyroid  and  the  exophthalmos  are  usually  on  the  same  side 
of  the  body  ;  but  this  is  not  always  the  case.  A  remarkable  case 
has  been  reported  and  figured  by  Dr  Burney  Yeo,  in  which  the 
exophthalmos  was  limited  to  the  left  eye  and  the  enlargement  of 
the  thyroid  to  the  right  lobe. 

In  my  scries  of  79  cases,  the  thyroid  was  enlarged  (when  the 
patient  came  under  my  notice)  in  71  cases  ;  there  was  no  enlarge- 
ment in   5  cases  (in  one  of  these  cases,  the  gland  had  been,  at  a 


EXOPHTHALMIC   GOITRE.  393 

previous  stage  of  the  case,  enlarged).  In  the  72  cases  in  which  the 
thyroid  was  (or  had  been)  enlarged,  the  enlargement  was  very- 
slight  in  8  cases,  and  more  or  less  considerable  (but  very  rarely 
great)  in  64  cases. 

In  the  71  cases  in  which  the  thyroid  was  enlarged  when  the 
patients  came  under  my  notice,  the  enlargement  was  symmetrical 
in  36  cases,  the  right  lobe  was  more  enlarged  than  the  left  in  28 
cases,  and  the  left  lobe  more  than  the  right  in  7  cases. 

In  the  71  cases  in  which  the  thyroid  was  enlarged,  the  con- 
sistency of  the  gland  was  soft  in  36  cases,  firm  or  hard  in  19  cases, 
and  not  noted  in  16  cases. 

Murmurs  were  present  over  the  enlarged  thyroid  in  23  cases, 
absent  in  35  cases,  and  not  noted  in  13  cases. 

Thrills  were  present  over  the  enlarged  thyroid  in  21  cases, 
absent  in  36  cases,  and  not  noted  in  14  cases. 

The  degree  of  enlargement,  like  the  prominence  of  the  eyeballs, 
undoubtedly  varies  from  time  to  time.  I  am  satisfied  that  a 
decided  increase  can  in  some  cases  be  observed  during  emotional 
excitement.  In  some  cases,  the  enlargement  of  the  thyroid  in- 
creases and,  in  others,  diminishes  during  menstruation  or  im- 
mediately after  menstruation.  In  Case  XX.  of  my  series,  in  which 
the  disease  developed  a  few  months  after  the  first  menstruation  and 
in  which  the  menstruation  was  irregular  in  time,  the  enlargement 
•of  the  thyroid  and  the  prominence  of  the  eyeballs  subsided  and 
almost  entirely  disappeared  during  the  menstrual  period  ;  if  the 
patient  went  longer  than  four  weeks  without  menstruating,  the 
prominence  of  the  eyeballs  and  the  enlargement  of  the  thyroid 
became  much  more  marked.  Temporary  enlargements  of  this 
kind  are  no  doubt  due  to  temporary  dilatation  of  the  thyroidal 
vessels. 

Prominence  of  the  Eyeballs. — The  exophthalmos  is  usually 
developed  simultaneously  with  the  enlargement  of  the  thyroid  and 
later  than  the  increased  frequency  of  the  heart.  The  degree  of 
prominence  varies  considerably  in  different  cases.  In  typical 
cases,  the  prominence  of  the  eyeballs  is  very  striking  and  char- 
acteristic. In  exceptional  cases,  there  is  no  exophthalmos.  When 
the  exophthalmos  is  great,  and  especially  when  the  upper  lid  is  at 
the  same  time  spasmodically  retracted,  the  countenance  acquires  a 
wild,  staring  look.  The  protrusion  of  the  eyeballs  is  occasionally  so 
great  that  the  insertions  of  the  recti  muscles  are  exposed  ;  and 
cases  have  actually  been  reported  in  which  it  was  said  that  the 
exophthalmos  was  so  extreme  that  the  eyeball  was  dislocated  out 
of  the   orbit,  and   had   to  be  pushed  back   into  its  place   by  the 


394  DISEASES   OF   THE    BLOOD   GLANDS. 

fingers.  As  I  have  already  stated,  the  exophthalmos  is,  in  rare 
cases,  unilateral. 

The  degree  of  prominence  appears  to  vary  from  time  to  time, 
as  the  result  of  emotional  excitement,  etc.  It  must,  however,  be 
remembered  that  in  many  cases  the  increased  protrusion  which 
appears  to  result  from  excitement  is  apparent  only,  and  due  to  the 
fact  that  under  excitement  the  upper  lid  becomes  more  retracted 
and  a  larger  portion  of  the  sclerotic  exposed  than  under  ordinary 
conditions. 

It  is  said  that  in  some  cases  the  eyeballs  are  actually  enlarged, 
but  if  such  is  the  fact,  the  degree  of  enlargement  is  probably 
inconsiderable. 

In  my  series  of  79  cases,  prominence  of  the  eyeballs  was 
present  in  64  cases,  absent  in  14  cases,  and  not  noted  in  1  case. 
In  the  64  cases  in  which  the  eyeballs  were  prominent,  the  ex- 
ophthalmos was  more  or  less  considerable  in  55  cases,  and 
very  slightly  marked  in  9  cases.  In  2  cases,  one  eye  only  was 
prominent. 

In  those  cases  in  which  the  exophthalmos  is  so  great  that  the 
lids,  when  closed,  are  unable  completely  to  cover  the  eyeball,  con- 
junctivitis or  ulceration  of  the  cornea  may  be  ultimately  produced. 
Mr  George  Berry  states  that  a  certain  degree  of  anaesthesia  of  the 
cornea  is  sometimes  present ;  and  he  suggests  that  it  is  a  symptom 
which  deserves  special  attention,  since  it  may  favour  the  production 
of  ulceration  of  the  cornea. 

In  the  great  majority  of  cases  of  exophthalmic  goitre — provided 
of  course  that  the  cornea  is  not  ulcerated,  but  this  condition  is 
extremely  rare — vision  is  unaffected.  The  retinal  vessels  are  in 
some  cases  dilated,  and  pulsation  in  the  retinal  arteries  can,  it  is 
said,  in  some  cases  be  seen  with  the  ophthalmoscope. 

Increase  of  the  orbital  fat  and  dilatation  and  engorgement  of 
the  vessels  at  the  back  of  the  orbit  are  usually  considered  to  be  the 
chief  causes  of  the  exophthalmos.  Spasm  of  the  fibres  of  Midler's 
muscle  is  another  condition  to  which  the  prominence  of  the  eyeballs 
has  been  attributed. 

The  Condition  of  the  Pupil. — The  pupils  are,  as  a  rule,, 
normal  in  size  and  in  many  cases  extremely  mobile.  Marked  and 
persistent  dilatation,  though  it  occasionally  does  occur,  is  rare.  In 
some  cases  the  pupils  are  unequal  in  size,  but  this,  too,  is  in  my 
experience  very  exceptional. 

The  absence  of  any  marked  and  persistent  dilatation  of  the 
pupils  is  strongly  opposed  to  the  view  that  the  disease  is  due  to 
irritation  of  the  cervical  sympathetic. 


EXOPHTHALMIC   GOITRE.  395 

In  my  series  of  79  cases,  the  condition  of  the  pupils  is  noted  in 
72  cases  ;  in  $7  cases  the  pupils  were  of  medium  size  ;  in  25  cases 
contracted  ;  and  in  10  dilated. 

Before  leaving  the  condition  of  the  eyeballs  it  may  perhaps  be 
well  to  refer  to  some  of  the  other  ocular  symptoms  which  are 
frequently  present. 

Stellwag's  sign. — In  many  cases,  the  upper  eyelid  is  spasmodi- 
cally retracted  and  the  aperture  between  the  eyelids  is  wider  than 
normal.  This  spasmodic  retraction  of  the  upper  lid  (which  is 
admirably  seen  in  Plates  XLIX.  and  L.,  Fig.  1,  of  my  Atlas  of 
Clinical  Medicine)  varies  in  degree  from  time  to  time,  and  is  often 
markedly  increased  under  emotional  excitement.  This  retraction 
of  the  upper  lid  goes  by  the  name  of  Stellwag's  sign,  and  appears 
to  be  due  to  spasmodic  contraction  of  Miiller's  muscle.  Its  diag- 
nostic value  is  considerable,  since  it  does  not  appear  to  occur  in 
other  forms  of  exophthalmos.  But  it  must  not  be  supposed  that 
this  (Stellwag's)  symptom  is  a  constant  feature  of  the  disease. 
Further,  I  have  met  with  it  in  a  few  other  cases  in  which  there  was 
no  suspicion  of  exophthalmic  goitre  ;  it  cannot,  therefore,  be  con- 
sidered pathognomonic. 

In  my  series  of  79  cases,  the  presence  or  absence  of  Stellwag's 
symptom  is  noted  in  70  cases  ;  it  was  present  in  37  and  absent  in 
33  cases. 

In  some  cases,  an  absence  of  reflex  blinking  has  been  observed. 
This  is  perhaps  due  to  the  spasmodic  retraction  of  the  upper  lid,  or 
to  anaesthesia  of  the  cornea. 

Von  Graefe's  sign. — In  many  cases  of  exophthalmic  goitre,  the 
upper  lid  fails  to  follow  the  eyeball  downwards  in  a  steady  co- 
ordinate manner  ;  the  movement  of  the  lid  hangs  fire,  as  it  were,  or 
follows  the  downward  movement  of  the  eyeball  in  an  uncertain, 
jerky  manner.  In  health,  the  downward  movement  of  the  eyeball 
is  accompanied  by  a  simultaneous  and  exactly  co-ordinated  move- 
ment of  the  upper  lid.  If  one  stands  in  front  of  a  healthy  individual 
and  makes  him  fix  and  follow  one's  finger  with  his  eye,  as  it  is 
moved  slowly  from  above  the  horizontal  line  of  vision  downwards 
towards  the  ground,  it  is  seen  that  as  the  eye  is  depressed  the  upper 
lid  moves  simultaneously  with  the  ball. 

In  my  series  of  79  cases,  the  presence  or  absence  of  Von  Graefe's 
symptom  is  noted  in  69  cases  ;  it  was  present  in  30  cases  and  absent 
in  39  cases. 

Other  ocular  derangements. — Mobius  has  pointed  out  that  in  a 
considerable  proportion  of  cases  of  exophthalmic  goitre  the  patient 
is  unable  to  converge  for  near  objects.      Ophthalmoplegia  externa,  or 


396  DISEASES   OF   THE   BLOOD   GLANDS. 

paralysis  of  one  or  more  of  the  external  muscles  of  the  eyeball,  has 
occasionally  been  observed. 

In  my  series  of  79  cases,  the  ability  to  converge  for  near 
objects  was  noted  in  43  cases;  in  17  of  these  cases,  the  power  of 
convergence  was  impaired  or  lost ;  and  in  the  remaining  26  cases 
was  normal. 

In  3  of  my  79  cases,  ophthalmoplegia  externa  was  present ;  in 
2  cases  the  degree  of  paralysis  was  slight ;  in  1  case  very  marked. 

Muscular  tremor. — This  symptom,  which  was  first  particularly 
described  by  Marie  and  Charcot,  is  highly  characteristic.  The 
tremor  consists  of  fine  rhythmical  muscular  movements  which 
appear  to  be  nearly  twice  as  rapid  (eight  or  nine  per  second)  as 
those  which  produce  the  tremor  of  paralysis  agitans  (in  which  the 
muscular  contractions  number  four  or  five  per  second). 

The  tremor  usually  affects  the  muscles  of  the  lower  limbs  and 
of  the  trunk  as  well  as  those  of  the  upper  extremities.  In  many 
cases  the  whole  body  can  be  felt  to  shake,  when  the  hand  is  placed 
on  the  top  of  the  head  or  on  the  shoulder.  According  to  Charcot, 
the  individual  digits  do  not  tremble,  but  I  am  not  satisfied  that  this 
statement  is  always  correct.  This,  he  states,  is  a  point  of  distinction 
between  the  tremor  of  exophthalmic  goitre  and  that  due  to  alcohol 
and  general  paralysis  of  the  insane,  in  which  conditions  the  tremor 
is  also  very  rapid  (eight  or  nine  per  second).  In  rare  cases,  the 
tremor  is  said  to  be  unilateral  ;  personally,  I  have  never  observed 
this.  I  am  in  the  habit  of  demonstrating  the  tremor  to  my  students 
by  making  the  patient  hold  out  the  arm  at  right  angles  to  the  body, 
and  then  balancing  a  stethoscope,  with  the  chest  end  uppermost,  on 
the  back  of  the  hand. 

In  some  cases,  in  addition  to  the  fine  rhythmical  tremor  which 
has  just  been  described,  irregular  jerking  spasmodic  movements  of 
the  fingers  and  also  of  the  toes  may  be  noted  if  carefully  looked  for. 

The  muscular  tremor  is  not  usually  developed,  at  all  events  in 
a  sufficient  degree  to  be  readily  perceived,  until  the  other  symptoms 
of  the  disease  (palpitation,  etc.)  have  become  pronounced;  but,  in 
some  cases,  it  appears  to  be  the  first  symptom  to  be  developed. 

The  tremor  is  of  considerable  diagnostic  importance,  especially 
in  some  of  the  imperfectly  developed  forms  of  the  disease  in  which 
there  is  no  enlargement  of  the  thyroid  and  no  exophthalmos. 

In  my  series  of  79  cases,  fine  tremors  were  present  in  66  cases, 
absent  in  5  cases,  and  not  noted  in  8  cases. 

General  nervousness. — Nervousness,  excitability  and  irritability 
are,  as  I  have  already  stated,  constant  and  highly  characteristic 
features    of  the    disease.     The    contrast    in    this   respect   between 


EXOPHTHALMIC   GOITRE.  397 

exophthalmic  goitre  and  myxcedema  is  very  striking  and  highly 
suggestive. 

In  my  series  of  79  cases,  general  nervousness  was  present  in  jj 
cases  (in  two  of  these  cases  the  nervousness  was  very  slight),  and 
not  noted  in  2  cases. 

Secondary  Symptoms  of  Exophthalmic  Goitre. — In  addition 
to  the  five  great  primary  symptoms  to  which  I  have  just  referred,, 
quite  a  number  of  other  symptoms  may  be  present. 

In  describing  the  "secondary"  symptoms  of  Graves'  disease,  I 
do  not  propose  to  follow  in  regular  sequence  the  order  of  the  symp- 
toms as  set  forth  in  Table  11  (see  p.  386).  In  that  table,  the 
symptoms  are  arranged  in  accordance  with  the  particular  system 
(integumentary,  digestive,  urinary,  etc.)  to  which  they  belong.  It 
is  preferable,  I  think,  to  regard  the  manner  in  which  the  symptoms 
are  produced,  rather  than  the  special  organ,  part  of  the  body,  or 
"  system  "  which  they  implicate.  Almost  all  the  "  secondary " 
symptoms  of  Graves'  disease  are  the  result  of  derangement  of  some 
part  of  the  nerve  apparatus.  Even  the  diarrhoea,  which  is  in  some 
cases  a  very  striking  symptom,  is  clearly  due  to  perverted  inner- 
vation. 

In  connection  with  the  exophthalmos,  I  have  already  referred 
to  two  of  the  most  common  and  important  of  the  secondary  symp- 
toms, namely,  Stellwag's  sign  and  Von  Graefe's  sign.  I  have  also, 
mentioned  the  not  unfrequent  occurrence  of  defective  convergence, 
and  the  occasional  occurrence  of  ophthalmoplegia  externa.  To  these 
conditions  I  need  not  further  refer. 

Many  of  the  secondary  symptoms  of  Graves'  disease  appear  to 
be  due  to  the  disturbance  of  the  vasomotor  nerve  apparatus. 

Excessive  Sweating-,  Subjective  Sensations  of  Heat,  Eleva- 
tions of  Temperature. — Excessive  sweating  is  a  very  characteristic 
and  constant  symptom.  During  the  attacks  of  sweating,  the  skin 
is  often  warm  as  well  as  moist.  In  many  cases,  sensations  of 
warmth  and  flushings  of  the  face,  feet,  hands  or  body  generally  are 
complained  of;  and  in  some  cases,  though  this  is  exceptional,  dis- 
tinct rises  of  temperature,  which  are  apparently  of  nervous  origin, 
for  they  may  occur  independently  of  any  discoverable  local  in- 
flammation or  visceral  complication,  occur.  They  are  said  to  be 
more  common  at  the  menstrual  periods.  In  rare  cases,  these  eleva- 
tions of  temperature  appear  to  be  associated  with  grave  cerebral 
symptoms,  though  no  case  of  the  kind  has  come  under  my  own 
notice. 

In  my  series  of  79  cases,  excessive  sweating  -was  present  in  64 
cases,  absent  in  7  cases,  and  not  noted  in  8  cases.     Flushings  were 


39S  DISEASES   OF   THE   BLOOD   GLANDS. 

present  in  40  cases,  absent  in  10  cases  and  not  noted  in  29  cases. 
In  18  of  the  79  cases  (all  hospital  patients),  the  course  of  the  tem- 
perature was  carefully  observed  ;  in  4  of  these  18  cases,  the  tempera- 
ture was  subnormal  ;  in  5  normal  ;  and  in  the  remaining  9  cases 
(in  which  the  temperature  was  usually  normal  or  subnormal) 
elevations  of  temperature,  for  which  there  was  no  apparent  cause 
(other  than  the  nervous  disturbances  associated  with  the  disease), 
and  which  were  usually  of  temporary  duration,  occurred. 

Diminished  Electrical  Resistance  of  the  Skin. — In  cases  of 
exophthalmic  goitre  the  resistance  which  the  skin  offers  to  the 
passage  of  electrical  currents  is  markedly  diminished  ;  this  appears 
to  be  due  to  the  fact  that  the  epidermis,  which  in  the  dry  state  is 
such  a  bad  conductor  of  electricity,  is,  in  consequence  of  vasomotor 
alterations  and  the  dilatation  of  the  capillary  vessels  which  results 
therefrom,  bathed  in  fluid,  its  resisting  power  to  electric  currents 
being  thereby  greatly  reduced. 

Dr  Wolfenden  (quoted  by  Sajous)  found  that  the  average  resist- 
ance of  the  normal  skin  to  the  passage  of  a  galvanic  current  of 
moderate  strength  was  from  4,000  to  5,000  ohms,  while  in  eight 
cases  of  exophthalmic  goitre  the  resistance  which  the  body  (skin) 
offered  to  the  passage  of  the  same  strength  of  current  was  only  500 
to  700  ohms  ;  in  two  of  these  cases,  the  resistance  was  as  low  as  200 
and  300  ohms  respectively.  The  measurements  are,  of  course, 
made  by  means  of  an  accurately  graduated  galvanometer  or  gal- 
vanoscope. 

Diminished  electrical  resistance  of  the  skin  is  not  peculiar  to 
Graves'  disease  ;  it  occurs  in  many  other  conditions,  such  as  chronic 
alcoholismus  and  acromegaly,  in  which  the  superficial  capillaries  are 
dilated  and  the  skin  bathed  in  moisture.  But,  so  far  as  I  know, 
such  an  extreme  degree  of  diminution  as  that  noted  by  Wolfenden 
in  exophthalmic  goitre  has  not  been  as  yet  observed,  except  as  a 
mere  temporary  occurrence,  in  other  diseased  conditions. 

Diarrhoea. — In  some  cases  of  exophthalmic  goitre,  diarrhoea  is 
a  prominent  symptom.  The  characters  of  the  diarrhoea  are  pecu- 
liar;  it  is  apt  to  occur  in  paroxysms,  suddenly  and  without  any 
apparent  cause  ;  it  usually  persists  for  several  days  and  then  spon- 
taneously disappears.  The  motions  are  frequent,  copious  and 
watery  ;  in  one  of  my  cases  the  motions  were  of  a  pinkish  colour, 
probably  due  to  the  presence  of  blood.  The  diarrhoea  is  usually 
unattended  by  pain  or  colic  ;  but  in  some  cases  colicky  pains  are 
complained  of  immediately  before  the  evacuations  take  place.  In 
one  of  Charcot's  cases,  the  attacks  of  diarrhoea  recurred  at  regular 
periodic  intervals.     During  the  attacks  of  diarrhoea,  the  tongue  may 


EXOPHTHALMIC   GOITRE.  399 

be  quite  clean  and  the  appetite  unimpaired ;  indeed  the  appetite  may 
be  increased,  even  voracious,  during  the  attacks.  In  some  cases,  the 
diarrhoea  is  not  easily  restrained  by  ordinary  astringent  remedies, 
such  as  laudanum.  When  the  diarrhoea  is  severe,  a  good  deal  of 
exhaustion  may  result.  It  seems  probable  that,  in  many  cases  of 
exophthalmic  goitre,  the  diarrhoea  is  of  nervous  origin,  and,  like  the 
sweating,  due  to  some  vasomotor  derangement. 

In  rudimentary  or  imperfectly  developed  cases  of  exophthalmic 
goitre,  the  diarrhoea  may  be  of  diagnostic  value,  just  as  the  gastric 
and  intestinal  crises  are  of  diagnostic  value  in  some  obscure  and 
undeveloped  cases  of  locomotor  ataxia. 

In  my  series  of  79  cases,  the  bowels  were  regular  in  38  cases  and 
constipated  in  1 1  cases  ;  in  2 1  cases  occasional  attacks  of  (nervous) 
diarrhoea  occurred  ;  in  9  cases  the  condition  of  the  bowels  is  not 
mentioned  in  the  notes. 

Vomiting-. — In  other  cases,  vomiting,  apparently  of  nervous 
origin,  occurs.  Dr  Dreschfeld  states  that  in  some  cases  of  this 
kind  the  breath  has  the  sweet  apple-like  odour  characteristic  of 
acetonemia,  and  that  the  urine  contains  diacetic  acid. 

In  my  79  cases,  vomiting  was  absent  in  46  cases,  present  occa- 
sionally in  9  cases,  and  not  noted  in  24  cases. 

Pigmentation  of  the  Skin. — Dr  David  Drummond  in  parti- 
cular has  directed  attention  to  this  condition  which  is  developed  in 
a  considerable  proportion  of  cases  of  Graves'  disease.  In  some 
cases,  the  pigmentary  deposits  are  distributed  in  patches,  a  common 
situation  being  round  the  orbits  ;  in  others,  the  whole  skin  is  uni- 
formly discoloured,  the  pigmentation  being  most  marked  in  those 
situations,  such  as  the  areolae  of  the  nipples  and  the  genital  organs, 
in  which  pigment  is  normally  most  abundant.  In  several  cases 
which  have  come  under  my  own  notice,  the  dirty,  dingy,  yellowish- 
brown,  or  earthy  tint  of  the  face  was  very  striking.  In  one  of  these 
cases,  the  disease  existed  in  a  rudimentary  form,  the  enlargement 
of  the  thyroid  and  the  prominence  of  the  eyeballs  being  absent.  I 
am  disposed  to  think  that  the  skin  pigmentation  is  in  some  cases 
of  considerable  diagnostic  value. 

In  my  series  of  79  cases,  abnormal  pigmentation  of  the  skin 
was  present  in  29  cases,  absent  in  39  cases,  and  not  noted  in  1 1 
cases. 

Patches  of  leucoderma,  urticaria,  and  other  skin  eruptions  have 
been  observed  in  some  cases  of  exophthalmic  goitre  ;  and  in  this 
connection  it  is  interesting  to  note  that  in  some  cases  of  Addison's 
disease  leucoderma  is  also  present. 

In  a  considerable  proportion  of  cases  the  hair  becomes  thin ; 


400  DISEASES   OF   THE   BLOOD   GLANDS. 

atropine  changes  in  the  nails  also  occasionally  occur,  but  in  my 
experience  appear  usually  to  be  due  to  anaemia  associated 
with  the  exophthalmic  goitre,  rather  than  to  the  exophthalmic 
goitre  itself. 

In  my  series  of  79  cases,  a  skin  eruption  was  present  in  8  cases, 
absent  in  45  cases,  and  not  noted  in  26  cases.  In  the  8  cases 
in  which  a  skin  eruption  was  present,  the  eruption  was  leucoderma 
in  3  cases,  eczema  in  2  cases,  erythema  in  2  cases  and  psoriasis  in 
1  case. 

Loss  of  hair  was  present  in  14  cases,  absent  in  14  cases  and 
not  noted  in  51  cases. 

Urinary  derangements. — Polyuria,  albuminuria  and  glycosuria 
occasionally  occur.  In  two  of  my  cases  in  which  the  amount  of 
albumen  was  considerable,  there  were  no  tube  casts  and  none  of 
the  ordinary  symptoms  of  Bright's  disease ;  and  it  is  perhaps 
worth  noting  that  in  both  of  these  cases  ophthalmoplegia  externa 
was  present.  It  is  probable  that  these  urinary  derangements, 
which  are  usually  merely  temporary  and  intermittent,  are,  like  so 
many  of  the  other  symptoms,  due  to  vasomotor  alterations.  As 
has  been  already  stated,  Dreschfeld  found  diacetic  acid  in  some 
cases  during  the  attacks  of  (?  nervous)  vomiting. 

If,  as  seems  probable,  the  nerve  centres  in  the  medulla  oblon- 
gata are  deranged  (either  primarily  or  secondarily)  in  cases  of 
exophthalmic  goitre,  the  occasional  occurrence  of  glycosuria  (and 
I  may  perhaps  also  add  of  polyuria  and  albuminuria)  is  not  difficult 
of  explanation. 

In  my  series  of  79  cases,  the  urine  was  normal  in  64  cases  ; 
albumen  (only  a  trace  in  4  cases)  was  present  in  6  cases,  and  not 
noted  in  9  cases. 

Respiratory  derangements. — A  short,  dry  {nervous)  cough  is 
sometimes  present.  In  one  of  my  cases,  a  profuse,  pink,  watery 
secretion  was  poured  out  from  the  bronchial  mucous  membrane. 
The  pulmonary  cedema  and  profuse  bronchial  secretion  in  that  case 
appeared  to  be  the  immediate  cause  of  death.  I  have  always 
regarded  the  pulmonary  cedema  and  the  profuse  bronchial  secre- 
tion which  were  present  in  this  case,  as  the  result  of  vasomotor 
paralysis.  The  condition  was,  I  believe,  exactly  comparable  to  the 
profuse  sweating  and  copious  diarrhoea  to  which  I  have  already 
referred. 

In  my  series  of  79  cases,  cough  was  present  in  12  cases,  absent 
in  44  cases  and  not  noted  in  23  cases. 

Increased  frequency  of  the  respirations  is  not  uncommon.  In 
some  cases  it  seems  to  depend  upon  ansemia  or  cardiac  complica- 


EXOPHTHALMIC   GOITRE.  40 1 

tions  ;  in  others  to  be  of  nervous  origin.  Diminished  expansion  of 
the  chest  during  inspiration  has  been  observed  in  some  cases 
(Bryson's  symptom). 

Nervous  derangements  not  previously  described. — Psychical 
symptoms  are  prominent  in  some  cases  of  Graves'  disease.  I  have 
already  referred  to  the  nervous  irritability  and  unrest.  The  least 
thing  "  puts  the  patient  into  a  tremble."  The  most  casual  observer 
cannot  fail  to  be  struck  with  the  extreme  "nervousness"  of  patients 
suffering  from  exophthalmic  goitre.  Their  nervous  equilibrium  is 
eminently  unstable.  Little  things,  which  would  be  unnoticed  by 
any  ordinary  individual,  are  sufficient  to  agitate  and  disturb  them. 
They  are  fidgety  and  irritable.  And  yet,  they  are  not,  as  a  rule, 
hysterical.  Charcot,  indeed,  states  that  some  patients,  who,  prior 
to  the  onset  of  the  disease,  were  distinctly  hysterical,  cease  to  be 
so  when  the  symptoms  of  Graves'  disease  become  fully  developed  ; 
he  further  states  that,  with  the  decline  of  the  disease  and  the  dis- 
appearance of  its  characteristic  symptoms,  hysterical  manifestations 
may  again  make  their  appearance  ;  but,  in  some  cases,  hysterical 
manifestations  are  undoubtedly  developed  during  the  course  of  the 
disease. 

Mental  alterations  of  a  more  decided  kind are  sometimes  observed, 
such  as  mania,  melancholia,  and,  more  rarely,  general  paralysis  of 
the  insane. 

Headache  is  a  frequent  symptom.  The  condition  of  sleep  varies  ; 
in  some  it  is  bad,  in  others  good  ;  in  some  cases  the  patients  com- 
plain of  unpleasant  dreams.  Neuralgia  is  not  uncommon.  Mig- 
raine, angina  pectoris,  epilepsy  and  chorea  are  occasionally  developed 
in  the  course  of  the  disease.  Charcot  mentions  the  occurrence  of 
paraplegia,  which,  he  states,  presents  certain  characters  which  seem 
to  show  that  it  is  peculiar  to  the  disease.  The  paralysis  is  usually 
incomplete  ;  but  in  one  case  it  was  complete  and  absolute  at  the 
time  of  the  patient's  admission  to  hospital ;  in  that  case,  the  para- 
lysed muscles  were  flaccid  and  moderately  atrophied  ;  the  reflexes, 
both  deep  and  superficial,  were  abolished  ;  the  electrical  reactions 
were  normal  ;  there  were  no  fibrillary  twitchings  ;  sensibility  was 
unimpaired,  and  the  bladder  and  rectum  were  unaffected.  In  those 
■cases  in  which  the  paralysis  was  incomplete  and  the  patient  was 
able  to  move  about  (either  with  or  without  the  aid  of  crutches),  a 
sudden  giving  way  of  the  legs,  due  to  sudden  and  unexpected 
flexion  of  the  knees,  was  apt  to  occur  ;  this  sudden  failure  of  the 
legs  seems  to  be  a  characteristic  and  peculiar  feature  of  the  condi- 
tion. The  paraplegia  is  not  permanent ;  it  seems  to  be  functional ; 
the  absence   of  hysterical   symptoms    and    the    characters    of  the 

2  C 


402  DISEASES   OF   THE   BLOOD    GLANDS. 

paraplegia   itself  (especially  the    fact   that   there   are   no  sensory 
disturbances)  seem  to  show  that  it  is  not  hysterical. 

In  my  series  of  79  cases,  headache  was  complained  of  in  26  cases, 
was  absent  in  31  cases  and  was  not  noted  in  22  cases.  Sleep  was 
good  in  26  cases,  bad  in  35  cases  (in  2  of  these  cases  there  were 
unpleasant  dreams),  excessive  in  1  case  and  not  noted  in  17  cases. 
Neuralgia  was  complained  of  in  10  cases,  absent  in  39  cases  and 
not  noted  in  30  cases. 

The  general  health ;  condition  of  appetite,  etc. — In  some 
cases  of  exophthalmic  goitre,  the  general  health  is  comparatively 
little  affected,  though,  as  I  have  already  said,  general  nervousness 
is  always  a  prominent  symptom.  Languor,  debility,  and  inability 
for  sustained  exertion  are  usually  very  marked  features.  In  most 
cases,  there  is  some  loss  of  flesh,  and  in  some  cases,  more  especially 
acutely  developed  cases  and  severe  cases,  there  is  marked  emaciation  ; 
in  others,  especially  in  the  later  stages  of  the  disease,  a  cachectic  con- 
dition is  developed.  If  I  may  judge  from  my  own  experience,, 
marked  debility,  great  emaciation  and  cachexia,  are  more  apt  to  be 
developed  in  the  early  stages  of  the  disease  in  those  cases  in  which 
the  patient  is  a  male.  In  many  cases  a  certain  degree  of  anaemia 
is  present. 

In  my  series  of  79  cases,  debility  was  present  in  74  cases  and 
not  noted  in  5  cases.  Anczmia  (usually  slight  in  degree)  was  present 
in  27  cases,  absent  in  37  cases  and  not  noted  in  15  cases.  Loss  of 
zveight  was  present  in  51  cases,  absent  in  14  cases  (in  1  case,  Case 
XXV.,  the  patient  got  fatter  as  the  disease  progressed)  and  not 
noted  in  14  cases.  In  several  cases,  the  loss  of  weight  was  con- 
siderable ;  in  Case  XV.,  the  patient  lost  16J  lbs.  ;  in  Case  XXI.,. 
14  lbs. ;  in  Case  XXIV.,  14  lbs. ;  in  Case  XL.  (this  patient  was  a 
male),  3  st.  10  lbs.  ;  in  Case  XLII.,  14  lbs.  ;  in  Case  XLIV.,  2  st.  ; 
in  Case  LXL,  U  st. ;  and  in  Case  LXXVL,  2  st.  3  lbs. 

In  some  cases,  the  appetite  remains  good  ;  in  others,  it  is  im- 
paired ;  in  others,  there  is  complete  anorexia  ;  occasionally  an  inor- 
dinate appetite  for  food,  or  sudden  fits  of  hunger,  occur  ;  in  other 
cases,  the  appetite  is  capricious  or  peculiar.  Loss  of  appetite,  dis- 
taste for  food,  and  complete  anorexia  arc  in  my  experience  usually 
associated  with  cachexia  and  emaciation.  Thirst  is  in  some  cases 
a  prominent  symptom. 

In  my  series  of  79  cases,  the  appetite  was  good  in  26  cases,  fair 
in  4  cases,  bad  in  28  cases,  excessive  in  4  cases,  and  not  noted  in 
17  cases. 

Jaundice  has  been  described  as  occurring  in  a  few  cases.  In  a 
male  case  of  rudimentary  or  imperfectly  developed  exophthalmic 


EXOPHTHALMIC   GOITRE.  403 

goitre  which  came  under  my  notice  some  twenty  years  ago  (but 
which  is  not  included  in  the  series,  for  I  have  unfortunately  mislaid 
the  notes),  the  motions  were  habitually  pale  and  devoid  of  bile.  Sir 
William  Jenner  seemed  to  attach  considerable  importance  to  this 
condition  as  a  sign  of  Graves'  disease. 

Menstrual  derangements. —  Amenorrhcea,  menorrhagia,  and 
irregularities  of  menstruation  occur  in  a  certain  proportion  of  cases  ; 
but  in  most  cases  of  exophthalmic  goitre  the  menstruation  is  quite 
natural.  Leucorrhoea  is  not  uncommon.  In  the  male,  loss  of  sexual 
power  or  even  complete  impotence  may  occur. 

In  my  series  of  79  cases,  the  condition  of  menstruation  is  noted 
in  65  cases.  In  these  65  cases,  the  menstruation  was  regular  and 
natural  in  29,  regular  and  scanty  in  5  cases,  irregular  in  2  cases, 
irregular  and  scanty  in  5  cases,  irregular  with  menorrhagia  in  3 
cases  ;  menorrhagia  was  present  in  5  cases  ;  amenorrhcea  in  5  cases  ; 
amenorrhcea  due  to  the  occurrence  of  the  menopause  in  8  cases ; 
amenorrhcea  due  to  pregnancy  in  1  case ;  in  1  case  the  patient 
(aged  14)  had  only  menstruated  once,  and  in  1  case  the  patient  (aged 
24)  had  never  menstruated. 

Other  Visceral  Derangements. — Enlargement  of  the  lymphatic 
glands  and  of  the  spleen  has  been  noticed  in  some  cases. 

Endocarditis  and  organic  valvular  lesions  are  occasionally,  but 
rarely,  developed.     Angina-like  pains  occasionally  occur. 

Asthenia,  asystole,  relative  and  muscular  incompetence  at  the  mitral 
or  tricuspid  orifices,  with  oedema  of  the  feet  and  general  dropsy,  and 
pulmonary  complications,  such  as  bronchitis  and  cedema  of  the 
lungs,  are  not  uncommon  in  the  later  stages  of  the  disease,  and  are 
often  the  immediate  cause  of  death. 

It  is  doubtful,  I  think,  whether  some  of  the  conditions  to  which 
I  have  just  referred  should  be  regarded  as  complications.  I  am 
disposed  to  think  that  many  of  them  are  the  direct  result  of  the 
disease,  due  to  the  same  nerve  derangements,  developed  in  a  very 
intense  form,  which  are  the  cause  of  the  other  symptoms  which  have 
been  previously  described. 

The  frequency  of  the  more  important  symptoms  in  my  series 
of  79  consecutive  cases  of  exophthalmic  goitre  is  shown  in  Table 
12. 

Course. — The  course  is  usually  chronic  ;  the  disease  generally 
persists  for  several  years  ;  some  cases  have  been  recorded  in  which 
the  symptoms  developed  very  rapidly  after  a  sudden  fright  or 
emotional  disturbance,  and,  after  being  present  for  a  short  time,  as 
rapidly  disappeared. 


404 


Table  12. — Showing  the  Relative  Frequency  of  the  More 


6 

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Apparent  Cause. 

0 

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0 

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0 

CO 

3 

s 

5 
1 

5 

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3 

s 

s 

1 

23 

F. 

s. 

S  months. 

Mental  anxiety. 

S. 

1 

D. 

0 

I 

1 

140 

1 

0 

2 

3 

20 

25 

F. 
F. 

s. 

M. 

2  years. 
2  years. 

Sleepine;  in  damp 

bed. 

0 

R. 
R. 

s. 
s. 

0 

1 

0 

1 

1 
1 

C. 

M. 

0 
0 

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1 
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120 
120 

1 
1 

0 

0 

4 

46 

M. 

12  years. 

0 

iV.S. 

R. 

□ 

0 

1 

C. 

0 

I 

160 

0 

0 

5 

28 

F. 

s. 

4&  years. 

0 

R. 

s. 

1 

1 

1 

M. 

I 

I 

0 

1 

1 

150 

1 

S.J 

6 

30 

F. 

M. 

(?) 

0 

S. 

iS. 

0 

I 

7 

20 

F. 

S. 

3  weeks. 

0 

s. 

I 

M. 

0 

0 

0 

I 

8 

14 

F. 

s. 

Some  months. 

0 

R. 

iS. 

D. 

0 

0 

0 

I 

1 

145 

0 

0 

9 

43 

M. 

1  year. 

0 

R. 

s. 

I 

M. 

I 

1 

0 

I 

140 

0 

0 

10 

24 

F. 

s. 

0 

S. 

I 

C. 

I 

0 

0 

I 

11 

5° 

F. 

M. 

S. 

I 

I 

I 

0 

I 

12 

33 

F. 

s. 

5  years. 

0 

S. 

I 

I 

I 

0 

1 

136 

13 

22 

F. 

s. 

2j  years. 

0 

L. 

F. 

I 

I 

I 

0 

I 

135 

S.W 

M 

38 

F. 

M. 

2  years. 

0 

R. 

F. 

1 

1 

0 

0 

0 

0 

I 

96 

15 
16 

23 
40 

M. 
F. 

M. 

2  years. 
6  years. 

0 
0 

iV.S. 

R. 

S. 

F. 

0 

0 

0 

I 

I 

c. 

0 

0 

] 

1  and 

ptosis. 

0 

I 
1 

150 

0 
iS. 

S.JV 
S.P 

J7 

17 

F. 

s. 

1  year. 

0 

s. 

I 

M. 

I 

0 

I 

120 

0 

0 

18 

19 
20 

34 

28 
13 

F. 

F. 
F. 

M. 

M.* 

S. 

Few  months. 

4 years:  married 

10  months. 
9  months. 

Loss  of  blood:  mis- 
carriage 7  months 
previously. 
0 

0 

s. 

R. 

s. 

F. 
S. 

1 
1 

1 
1 

I 

I 
I 

M. 

C. 
M. 

I 

I 
0 

0 

0 
0 

I 

0 
0 

I 

1 
I 

130 

140 
170 

0 

0 
0 

0 

0 
0 

21 

27 

F. 

S. 

7  years. 

0 

R. 

S. 

1 

1 

I 

C. 

I 

I 

I 

0 

I 

120 

0 

s.r 

22 

2;; 

45 
19 

F. 
F. 

M. 
S. 

20  years. 
2  years. 

After  birth  of  2nd 

child. 

0 

1  s. 

S. 
S. 

F. 
S. 

0 

1 

0 

1 

I 
I 

M. 
D. 

I 
I 

I 
0 

I 

0 
0 

I 
I 

96 
120 

0 

iS. 

0 

S.I 

24 

39 

F. 

S. 

4J  years. 

0 

L. 

S. 

1 

1 

I 

M. 

I 

I 

0 

I 

140 

0 

0 

25 

34 

F. 

s. 

6  months. 

0 

S. 

S. 

0 

0 

I 

M. 

I 

I 

0 

I 

120 

0 

0 

26 
27 
28 

42 
19 
35 

F. 
F. 
F. 

\v. 

s. 
s 

1  year. 
1  year. 
6  months. 

Mental  shock. 

0 

Influenza. 

0 

s. 
s. 

S. 
F. 

0 

1 

0 

1 

T 

iR. 

only 
1 

C. 
M. 
C. 

I 
I 
I 

0 
0 

I 

I 

0 
0 
0 

I 
I 
I 

0 

170 
86 

130 

I 
0 
0 

S.1V 

&1 

0 

0 

30 

28 
45 

F. 
F. 

s. 
s. 

4  months. 
i\  years. 

Endocarditis, 

'!  rheumatic. 

Influenza. 

0 

0 
R. 

0 
F. 

0 

0 
0 

1 

M. 
M. 

0 

I 

0 

1 

0 

I 

0 

0 

I 
I 

160 
r45 

0 

0 
0 

32 

46 
44 

F. 
F. 

M. 
S. 

6  years. 
10  years. 

Overwork  and 

mental  anxiety. 

0 

s. 

R. 

S. 
F. 

1 
0 

1 
0 

1 
oF. 

M. 

M. 

1 
O 

I 
0 

I 
0 

0 
0 

I 
I 

140 
160 

iS. 
iS. 

S.P 

&M 
0 

13 

49 

F. 

S. 

9  months. 

Menopause. 

L. 

S 

0 

C. 

O 

0 

0 

0 

I 

130 

0 

0 

•t 

3« 

M. 

Several  months. 

0 

R. 

s. 

1 

1 

1 

C. 

O 

0 

0 

0 

1 

120 

0 

S.  al 

35 

29 

F. 

M.* 

4  years. 

0 

R. 

s. 

1 

1 

1 

M. 

O 

0 

0 

I 

130 

I 

0 

36 

49 

F. 

M. 

16  years. 

0 

R. 

F. 

0 

0 

0 

M. 

° 

0 

0 

0 

I 

140 

0 

S.M 

7 

■■\ 

F. 

S. 

6  years. 

Mental  worry. 

s. 

s. 

0 

0 

iS. 

M. 

0 

0 

0 

I 

140 

0 

0 

3? 

30 

F. 

S. 

10  months. 

Influenza. 

S. 

s. 

0 

• ' 

1 

D. 

1 

1 

I 

0 

1 

140 

0 

0 

■-.' 

44 

F. 

M. 

16  months. 

Mental  shock. 

s. 

■  > 

M. 

1  > 

1 1 

'  1 

0 

r 

0 

140 

0 

S.l| 

•I " 

r' 

M. 

1  year. 

Over-exertion, 
shooting. 

R. 

s. 

" 

0 

1 

M. 

0 

I 

0 

0 

I 

1 

no 

0 

S.M 

Important  Symptoms  in  79  Cases  of  Exophthalmic  Goitre. 


u  3  0 

^  "s'S 

O      Ul     X 

«  £w 

E   5  c 

S6° 
0     1 

:/ 
3 
0 
O 

O 

c 

p 

0 
> 

■z. 

1 

0 

E 

V 

H 

V 
CJ 

~i 
M 

X 
I 

ft 
O 

■5 

c 
0 

U 

'3 

-: 
a 
u 

-si 

(3  £ 

1" 

M 

3 

bi 

c 

% 

en 

V 

0 
c 
_o 

rt.c 

u  T. 

5b 

c 
0 

ft 

3 

.5 

'3 

0 
0 

6 

<v 
ft 
E 
<u 
H 

J5 

0 
0 

>> 
IS 
P 

1 

E 

ti 
c 
< 

1 

0, 
ft 
< 

G. 

% 

a 

n 

R. 

bi> 

'  = 
0 

> 

0 

P 

c 
.2 

3 
c 

0  oj 

B. 

O 

1 

0 

Psoriasis. 

1 

N. 

R. 

I 

0     1 

1 

0 

B. 

0 

O 

E. 

1 

1 

1 

B. 

D. 

0 

N. 

0 

D     * 

O 

1 

G. 

0 

O 

1 

0 

0 

1 

0 

G. 

R. 

0 

N. 

I.S. 

3 

3        I 

I 

1 

1 

O 

B. 

0 

O 

I 

1 

1 

0 

1 

1 

B. 

D. 

T.A. 

C         I 
I 

O 

1 
1 
1 
1 

1 
1 
1 

1 

0 

1 

1 
1 
1 

I 
O 

I 

B. 

'  ■ 

O 
O 

Impair,  of 
memory. 

I 

I 
I 
I 

1 

1 

0 

1 
1 

0 

0 

1 

1 

1 

0 

Leuco- 
derma. 

1 
1 

1 

1 

1 
1 
1 

1 
1 

P. 

R. 

R. 
D. 
D. 

D. 
R. 

0 

N. 

N. 
N. 

R.S. 

Once  only 
31110s.  ago 

R.S. 
I. 
R. 

0 

0 
0 

0 
0 
0 
0 
0 

I 

0 

1 

1 

B. 

0 

I 

1 

0 

0 

° 

16J  lbs. 

1 

P. 

D. 

1 1 

A. 

I 

I 

1 
1 

1 
i 

I 

B. 
B. 

0 

1 
1 

0 

0 

1 
1 

1 
1 

N. 

R. 

0 

I 
I 

0 
I 

1 

1 
1 

1 

1 
1 

B. 

B. 
B.D. 

0 

1 

1 
1 

0 

0 
0 

0 

1 

1 
1 

1 

1 
1 

B. 

D. 
R. 

N. 

N. 

R. 

R. 
I. 

4 

0 
0 

I 
I 

I 

1 
1 

1 
c 

G. 
G. 

0 
0 

I 

1 
1 

0 

i 

1 
14  lbs. 

1 

1 
1 

1 
0 

P. 

D. 
R. 

N. 
N. 

R. 
R. 

0 

9 

I 

O 

1 

I 

I 

B. 

0 

I 

1 

0 

0 

1 

1 

P. 

C. 

N. 

A. 

0 

I 
I 

1    I 

O 

O 

I 

1 
1 
1 

I 
I 
I 

I 

B. 
B. 

B. 

0 
0 
0 

I 
I 

1 
1 
1 

1 
0 

1 

0 
0 
0 

I 
Grey. 

1 

1 
14  lbs. 

0 
fatter. 

1 

1 

0 
0 

P. 
E. 
B. 

D. 
R. 
R. 

0 

1 

N. 
N. 
N. 

R. 
R. 
R. 

0 
0 
1 

I 

O 

1 

I 

I 

G. 

0 

1 

0 

0 

1 

1 

G. 

C. 

0 

N. 

R. 

0 

I 

I 

1 

I 

0 

1 

0 

1 

1 

0 

G. 

R. 

N. 

R.S. 

0 

I 

I 

1 

I 

I 

B. 

1 

0 

I 

1 

1 

0 

1 

1 

1 

1 

G. 

C. 

0 

N. 

I.S. 

0 

1 

O 

1 

I 

O 

0 

I 

1 

1 

1 

0 

F. 

D. 

0 

N. 

0 

I 

O 

1 

I 

1 

B. 

1 

0 

I 

1 

1 

0 

1 

1 

1 

P. 

D. 

N. 

R. 

0 

I 

I 

1 

I 

O 

B. 

0 

0 

I 

1 

0 

0 

1 

1 

1 

1 

B. 

D. 

1 

N. 

R.S. 

0 

O 

O 

1 

I 

I 

B. 

1 

0 

1 

1 

1 

1 

0 

G. 

R. 

0 

N. 

I.  men. 

0 

O 

1 

I 

0 

0 

r 

1 

1 

1 

1 

1 

0 

B. 

D. 

0 

T.A. 

I 

O 

1 

I 

I 

B. 

1 

0 

I 

1 

1 

1 

1 

1 

B. 

R. 

1 

N. 

R. 

1 

O 

O 

1 

I 

0 

G. 

0 

0 

0 

1 

0 

0 

1 

0 

B. 

R. 

0 

T.A. 

I.M. 

7 

O 
0 

O 
O 

1 
1 

I 
I 

I 
O 

B. 
G. 

0 
0 

0 
0 

I 
I 

1 
1 

1 
0 

Leuco- 

derma. 

0 

1 
0 

1 
1 

1 
1 

1 
1 

P. 

F. 

R. 

D. 

0 

N. 

N. 

N.M. 
A. 

0 
0 

J   I 

O 

1 

I 

I 

G. 

1 

0 

O 

0 

0 

0 

0 

1 

0 

G. 

R. 

0 

N. 

R. 

5 

0    3 

O 

1 

I 

O 

G. 

0 

0 

1 

1 

1 

0 

0 

1 
52  lbs. 

1 

0 

P. 

R. 

0 

N. 

Table  12 


Duration. 


9  years. 
3  years. 
Several  months 

2  years. 

11  months. 

3  months. 

10  years. 

2  years. 

1  year. 

4  years. 

iS  months. 
Some  months. 

3  years. 

9  months. 
9  years. 
18  months. 
3  years. 
2A  years. 

3  years. 

2  years. 

7  months. 
22  years. 
6  months. 
2  years. 

6  months. 
2  months. 
2  years. 

5  years. 

1  year. 

2  years. 

5  months. 
2  years. 

2  months. 

8  years. 

5  years. 

6  months. 

3  years. 

6  months. 
5  months. 


Apparent  Cause. 


Bronchitis 


Nervous  shock. 


Fright. 


Birth  of  only 
child. 


Influenza. 

Fright. 

Influenza. 

Typhoid  and 
fright. 
Grief. 


Privation  and 

starvation. 

Enlarged  thyroid 

since  9  years  old. 


Mental  shock. 
Mental  worry. 

Influenza. 

Mental  shock. 

o 

Mental  agitation. 

Loss  of  blood. 


Excessive  strain 
nursing. 


oF. 


1  S. 

1  s. 


1  v.s. 


Thyroid. 


X>  V 

0    C 

-i 


R. 

S. 

S. 

S. 

0 

0 

R. 

s. 

R. 

s. 

L. 

s. 

1  s. 


M. 
C. 
M. 
C. 
M 
M. 
C. 
M. 
M. 
C. 
D. 
M. 
C. 

c. 
c. 
c. 

M. 

c. 

M. 
C. 
C. 

c. 

M. 
D. 
M. 
M. 
M. 
5.  M. 
D. 
D 


I 

D. 

0 

M. 

0 

C. 

oF. 

C. 

1  R. 

M 

1 

D. 

0 

C. 

1 

M. 

Js  & 

c  >, 

Ol/l 

> 

5=5. 
I! 

c 

V 
> 

> 

S 

'5b 

U 

"art 
0  a 
E  v 
~3  x 
■SS 

-C 

a. 
O 

a 

3, 

0 

Mui 

c  — 

15  if, 
J| 

H 

>> 

0 
c 

0) 

3 
cr" 
<v 

& 

0) 

"3 

Ph 

0 

0 

0 

0 

0 

90 

I 

1 

0 

0 

96 

0 

0 

0 

0 

0 

130 

I 

1 

1 

0 

1 

140 

0 

0 

0 

0 

1 

150 

0 

0 

0 

0 

1 

140 

I 

1 

0 

0 

1 

120 

I 

1 

1 

1 

130 

0 

0 

0 

0 

1 

140 

0 

0 

0 

0 

0 

120 

I 

1 

0 

0 

1 

156 

0 

1 

0 

1 

120 

0 

0 

0 

0 

120 

I 

1 

0 

0 

1 

120 

I 

1 

1 
1 

1  S. 
1  S. 

1 
1 

104 
240 

0 

0 

0 

0 

0 

9S 

0 

0 

0 

0 

1 

140 

I 

1 

0 

1 

114 

I 

1 

0 

1 

108 

0 

1 

0 

1 
1 

126 

10S 

I 

1 

0 

0 

i 

no 

I 

1 

0 

1 

120 

0 

0 

0 

1 

no 
120 

1 

1 

0 

0 

90 

1 

0 

120 

0 

0 

0 

120 

0 

1 

1 
0 

0 
0 

120 
no 

0 

0 

1 

0 

150 

0 

0 

0 

0 

150 

0 

0 

0 

0 

140 

0 

0 

1 

0 

140 

I 

0 

1 

0 

120 

0 

0 

0 

0 

112 

0 

0 

0 

0 

120 

0 

0 

0 

0 

120 

'  S.  =  Slight;  V.S.  -  Very  slight.  -  S.  =  Symmetrical  ;  K.  =  Right  chiefly  enlarged  ;  L.  =  Left  chiefly  enlarged.  "S.  =  Sofl 
C.  =  Contracted;  M.=of  medium  size.  •  S.  =  Slight.  7S.  =  S!ight.  "  S.  =  Systolic;  M.  =  Mitral ;  P.  =  Pulrnonar> 
"'  Grey=  Became  grey  prematurely.  "  E.  =  Above  normal;  N.  =  Normal ;  S.N.  =  Subnormal.  12G.  =  Good;  F.  -  Fail 
able  albumen;  T.A.  =  Traces  of  albumen.  '■'•  K.  =  ReguIar;  I. S.  =  Irregular  and  scanty;  R.S.  =  ReguIar  and  scant> 
Amenorrhcea  due  to  menopause  ;  M.  =  Menorrhagia  ;  N.M.  =  Never  Menstruated  ;  P.  =  Pregnant. 


-Continued. 


407 


P.2 
o 

t/3 


■si 

ca  S 


B.D. 
B. 
G. 
B. 
B. 
G. 
B. 
G. 
E. 
B. 

G. 
G. 


Depres- 
sion. 


Depression 

and  impair. 

lemory. 


Erythema. 


Leuco- 
derma. 
Eczema. 


o     Erythema 


14  lbs. 


28  lbs. 


S.N. 

N. 

E. 
S.N. 
S.N. 

N. 

E. 
S.N. 

E. 

S.N. 

&E. 

E. 

N.  &E 

S.N. 

S.N. 


21  lbs. 


R. 


3I  lbs. 


G. 
B. 
B. 
B. 
G. 
B. 
G. 
G. 
E. 
G. 
E. 
P. 

G. 
G. 
G. 
G. 
B. 
E. 
G. 
G. 
F. 


N. 

N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
A. 
N. 
N. 

N. 
N. 
N. 
A. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 

N. 

N. 
N. 
N. 
N. 
N. 
N. 
N. 
N. 


Is 


R.S. 

R. 
A. 
A.  men. 
R. 
R. 
A. 
R. 
R. 
I.S. 
R. 

A. 
A.  men. 
A.  men. 
A.  men. 

R. 

P. 
R. 
R. 

A.  men. 
R. 
M. 
A. 
R. 
I.S. 
M. 
R. 
M. 

I.S. 

A.  men. 
R. 
R. 
I.M. 

R. 
A.  men. 

M. 
A.  men. 


3 
7 

3 

T 

(married 
5  years). 

1 
(3rd  m.). 

5 


F.  =  Firm  or  hard.  4  S.  =  Slight  ;  1  R.  only  =  Right  eye  only;  o  F.=Absent  when  seen,  formerly  present.  °  D.  =  Ddated; 
T.  =  Tricuspid;  D.  =  Diastolic  ;  S.  all  =  Systolic  murmur  in  all  the  areas.  °  B.=Bad;  B.D.  =Bad  with  dreams;  G.  =Good. 
P.=Poor;  E.  =  Excessive.  1S  R.  =  Regular  ;  C.  =  Constipated  ;  D.  =Occasional  diarrhoea.  '«  N.  =  Normal ;  A.=Consider- 
I.  =  Irregular  ;    A.  =  Amenorrhcea  ;    I.M.  =  Irregular  and   menorrhagia  ;    I.    men.  =  Irregular   due   to  menopause  ;    A.  men.— 


40s  diseases  of  the  blood  glands. 

Morbid  Anatomy  and  Pathology. 

From  the  foregoing"  description,  it  is  obvious  that  the  sympto- 
matology of  exophthalmic  goitre  has  of  recent  years  been  so  fully 
elaborated  that  we  may  now  be  said  to  possess  a  very  complete  and 
accurate  knowledge  of  the  clinical  features  of  the  disease.  The 
pathology  and  pathological  physiology  of  the  affection  are  in  a  very 
different  position,  for  as  yet  we  have  no  certain  knowledge  as  to  the 
exact  position  and  nature  of  the  lesion. 

The  most  striking  pathological  alteration  found  in  the  bodies  of 
patients  who  have  died  from  exophthalmic  goitre  is  the  enlargement 
of  the  thyroid  gland.  This  enlargement  is  not  merely  the  result  of 
increased  vascularity,  for  it  is  attended  with  an  increase  of  the 
glandular  tissue.  The  increase  is  not,  however,  a  simple  hyper- 
trophy. The  microscope  shows  that  the  normal  structure  of  the 
gland  is  materially  modified.  The  normal  cubical  epithelium  is 
replaced  by  epithelium  of  a  columnar  form,  resembling  more  in 
form  that  of  a  tubular  secreting  gland.  Catarrhal  changes  in  the 
epithelium  which  lines  the  glandular  spaces,  alterations  in  the 
colloid  material,  which  becomes,  it  is  said,  more  mucinous  in  char- 
acter, or  even  disappears  to  a  great  extent,  and  proliferation  and 
cellular  infiltration  of  the  connective  tissue  have  been  described  by 
Professor  Greenfield  and  Dr  Robert  Muir.  Greenfield  states  that 
in  some  cases  new-formed  tubules  are  developed  which  give  the 
structure  a  resemblance  to  that  of  the  salivary  gland.  In  two  of 
my  own  cases  very  similar  changes  were  present. 

The  heart  is  often  less  affected  than  one  would  expect  from  the 
very  marked  character  of  the  cardiac  disturbances  which  are  present 
during  life.  In  some  cases,  the  organ  is  normal  both  in  size  and 
weight  ;  in  others,  it  is  dilated  ;  in  others  again,  it  is  to  some 
extent,  but  not  usually  in  an)'  marked  degree,  hypertrophied. 
Organic  changes  in  the  valves  and  appearances  indicative  of  old  or 
recent  endocarditis  are  comparatively  rarely  met  with. 

According  to  some  observers  the  arteries  throughout  the  body 
are  dilated.     In  some  cases,  the  arterial  coats  have  been  thickened. 

The  thymus  gland  is  usually  (?  always)  persistent  and  enlarged. 
The  significance  of  this  fact  is  as  yet  unknown. 

The  orbital  fat  is  usually  increased  in  amount.  As  I  have  pre- 
viously stated,  the  exophthalmos  is  generally  thought  to  be  clue  to 
this  increase  and  to  the  dilated  condition  of  the  vessels  at  the  back 
of  the  orbit.  The  external  muscles  of  the  eyeballs  are,  it  is  said,  in 
some  cases  affected  with  fatty  degeneration. 

Pathological  chancres  have  also  been  described  in  the  cervical 


EXOPHTHALMIC   GOITRE.  409 

sympathetic,  the  floor  of  the  \th  ventricle,  etc.  ;  but  so  far  as  I  am 
able  to  judge,  such  alterations  are  in  no  way  characteristic  ;  some 
of  them  are  probably  mere  associated  or  accidental  alterations  ; 
others,  such  as  recent  haemorrhages,  which  have  been  met  with  in 
several  cases,  are  probably  the  result  of  the  profound  vasomotor 
and  vascular  alterations  which  are  such  prominent  features  in  the 
later  stages  of  severe  and  fatal  cases,  and  are  not  the  cause  of  the 
disease.  It  is  important,  however,  to  note  that  in  one  case  the  resti- 
form  body  was  atrophied  and  that  in  two  cases  (one  described  by 
Mendel  and  the  other  by  Marie  and  Marinesco)  the  solitary  bundle 
of  fibres  in  the  medulla  oblongata  was  atrophied. 

In  a  few  cases  the  lymphatic  glands  have  been  enlarged,  but 
this  change  is,  so  far  as  our  present  knowledge  enables  us  to 
judge,  inconstant  and  perhaps  merely  an  accidental  or  an  associated 
lesion. 

Pathological  Physiology. — The  exact  pathology  of  exoph- 
thalmic goitre  is  still  unsettled.  Many  different  theories  have  from 
time  to  time  been  advanced  to  account  for  the  phenomena  of  the 
disease. 

The  old  view,  which  for  long  held  the  field,  is  that  exophthalmic 
goitre  is  due  to  an  irritative  lesion  of  the  sympathetic  in  the  neck. 
The  widespread  character  of  the  symptoms  seems  opposed  to  the 
view  that  a  localised  lesion  of  the  sympathetic  in  the  neck  is  the 
primary  cause  of  the  disease.  Careful  microscopical  examination 
has  failed  to  show  that  the  thoracic  and  abdominal  portions  of  the 
sympathetic  are  the  seat  of  any  definite  and  constant  lesion  ; 
although  pathological  alterations  have  by  some  observers  been 
described  in  the  cervical  ganglia,  other  observers  have  found  these 
structures  entirely  normal.  Further,  the  absence  of  any  marked 
and  persistent  dilatation  of  the  pupils  is,  as  has  already  been  pointed 
out,  opposed  to  this  view.  Again,  some  of  the  symptoms  (such,  for 
example,  as  the  dilatation  of  the  blood  vessels,  which  is  usually 
thought  to  be  a  conspicuous  feature  of  the  disease)  seem  to  indicate 
a  paralytic  rather  than  an  irritative  lesion.  It  must,  however,  be 
remembered  that  Benedict  has  suggested  that  the  vascular  dilata- 
tion may  be  due  to  an  irritative  lesion  of  the  vaso-dilator  nerves> 
which  run  in  the  sympathetic. 

It  has  also  been  theorised  that  the  disease  is  due  to  the  pressure 
of  the  enlarged  thyroid  upon  the  cervical  sympathetic,  and  it  has 
recently  been  claimed  that  section  of  the  sympathetic  in  the  neck 
is  followed  by  disappearance  of  the  symptoms. 

Friedreich  theorised  that  a  paralytic  condition  of  the  vasomotor 
nerves,  by  causing  an  increased  flow  of  blood  through  the  coronary 


410  DISEASES   OF   THE    BLOOD   GLANDS. 

arteries    and    thereby    increasing    the    excitability    of  the  cardiac 
ganglia,  is  the  cause  of  the  increased  action  of  the  heart. 

A  lesion  of  the  nuclei  of  the  pneumo-gastric  nerves  and  the 
other  nervous  structures  in  the  medulla  oblongata  has  also  been 
suggested  as  a  cause  of  the  disease,  and,  as  has  already  been  stated, 
small  superficial  haemorrhages  have  been  described  by  more  than 
one  observer  as  occurring  in  the  floor  of  the  fourth  ventricle.  But 
I  see  no  reason  for  supposing  that  these  lesions  (haemorrhages)  were 
other  than  accidental  or  secondary  results  ;  such  haemorrhages  are 
by  no  means  uncommon  in  other  diseased  conditions,  and  their 
occasional  occurrence  just  before  death  in  a  disease  in  which  the 
vascular  and  vasomotor  alterations  are  so  profound  is  not  to  be 
wondered  at. 

Experimental  evidence  has  also  been  advanced  in  favour  of 
the  view  that  the  disease  is  due  to  disease  or  derangement  of 
the  medulla  oblongata.  Filene  and  Bienfait  state  that  sections 
in  the  neighbourhood  of  the  restiform  body  in  some  cases  result  in 
the  production  of  exophthalmos,  enlargement  of  the  thyroid  and 
tachycardia  ;  and  in  one  case  all  the  three  great  primary  symptoms 
'increased  frequency  of  the  heart's  action,  enlargement  of  the  thy- 
roid and  prominence  of  the  eyeballs)  were  simultaneously  developed. 
But  the  validity  of  these  experimental  observations  has  been 
vigorously  questioned. 

The  widespread  distribution  of  the  vasomotor  alterations,  the 
character  of  many  of  the  other  symptoms  (such  as  Von  Graefe's 
symptom,  Stellwag's  symptom,  defective  convergence  and  ophthal- 
moplegia externa),  and  the  fact  that  in  rare  instances  the  symptoms 
(such  as  the  exophthalmos  and  the  tremor)  are  unilateral,  are  highly 
suggestive  of  a  lesion  or  functional  disturbance  of  the  central  ner- 
vous system. 

But  even  granting  that  organic  or  functional  changes  of  this 
kind  are  actually  present,  it  does  not  necessarily  follow  that  they 
are  the  primary  cause  of  the  disease  ;  although  they  support,  they 
do  not  necessarily  prove,  its  nervous  origin. 

The  exact  cause  of  the  increased  frequency  of  the  heart's  action 
is  a  matter  of  dispute.  According  to  one  view,  it  is  the  result  of 
overaction  (irritation)  of  the  sympathetic ;  according  to  another,  of 
diminished  action  (paralysis)  of  the  vagus  ;  perhaps  both  views  are 
correct. 

The  theory  which  has  been  advanced  by  Mobius  and  strongly 
supported  by  Greenfield — that  the  primary  cause  of  the  disease  is 
the  lesion  ^hypertrophy)  of  the  thyroid  gland — is  very  plausible.  In 
support  of  this  view,  George   Murray  argues  that  the  condition  of 


EXOPHTHALMIC   GOITRE.  41 1 

the  thyroid  gland  in  exophthalmic  goitre  may  fairly  be  compared 
to  that  of  the  mammary  gland  during  lactation,  and  that  we  may 
reasonably  conclude  that  a  far  larger  quantity  of  thyroid  secretion 
is  poured  into  the  circulation  than  in  health. 

That  many  of  the  symptoms  of  exophthalmic  goitre  are  due  to 
an  excessive  or  perverted  secretion  of  the  thyroid  seems  to  me  to 
be  supported  by  the  following  facts  : — 

1.  Many  of  the  symptoms  of  exophthalmic  goitre  are  the  direct 
opposite  of  those  which  characterise  myxcedema  (see  below) ;  and, 
since  the  symptoms  of  myxcedema  are  due  to  defective  thyroid 
secretion,  it  is  reasonable  to  suppose  that  those  symptoms  of 
exophthalmic  goitre  which  are  the  direct  opposite  of  myxcedema 
are  due  to  an  excessive  or  perverted  thyroid  secretion. 

2.  In  some  cases  of  exophthalmic  goitre  the  enlargement  of  the 
thyroid,  after  persisting  for  a  time,  subsides,  the  gland  becomes 
atrophied  and  sclerosed  ;  and,  with  this  atrophy,  the  symptoms  of 
exophthalmic  goitre  disappear  and  those  of  myxcedema  are  deve- 
loped. 

Several  cases  of  this  kind  have  been  recorded.  Case  XVII.  (see 
page  354)  is  an  example  in  point. 

3.  In  some  cases  of  exophthalmic  goitre,  excision  of  the 
enlarged  thyroid  is  undoubtedly  followed  by  marked  improvement 
or  cure. 

The  Points  of  Contrast  between  Myxcedema  and  Exoph- 
thalmic Goitre. — In  a  paper  read  before  the  Medico-Chirurgical 
Society  of  Edinburgh  on  3rd  March  1891,  and  published  in  the 
"Transactions"  of  that  Society  (Vol.  x.,  p.  126),  and  in  my  Atlas 
of  Clinical  Medicine  (Vol.  i.,  p.  26),  I  was,  so  far  as  I  know,  the 
first  to  publicly  direct  attention  to  the  points  of  contrast  between 
myxcedema  and  exophthalmic  goitre.  The  more  important  points 
of  similarity  and  difference  are  as  follows  :— 

In  both  affections,  the  thyroid  gland  is  diseased,  and  both 
diseases  occur  much  more  frequently  in  women  than  in  men. 

But  the  character  of  the  thyroid  lesion,  the  mode  of  develop- 
ment and  the  nature  of  many  of  the  symptoms  are  very  different 
in  the  two  diseases. 

In  myxcedema,  the  thyroid  gland  is  atrophied  and  its  secreting 
structure  destroyed  ;  whereas  in  exophthalmic  goitre  the  thyroid 
gland  is  enlarged  and  its  secreting  structure,  though  modified  in 
character,  is  increased  in  quantity.  In  short,  in  myxcedema  the 
secretion  of  the  thyroid  gland  is  greatly  diminished  or  suppressed  ; 
whereas  in  exophthalmic  goitre  the  secretion  of  the  thyroid  gland 
is  (apparently)  increased  and  perhaps  altered  in  character. 


412  DISEASES   OF   THE   BLOOD   GLANDS. 

The  symptoms  of  myxoedema  are  almost  always  developed  in  a 
slow,  insidious,  and  gradual  manner  ;  *  whereas  the  symptoms  of 
exophthalmic  goitre  not  unfrequently  develop  with  considerable 
rapidity,  sometimes,  indeed,  suddenly,  after  a  fright  or  other  pro- 
found emotional  disturbance. 

Myxoedema  is  usually  developed  at  a  later  age  than  exoph- 
thalmic goitre.  The  ordinary  adult  form  of  myxcedema  is  usually 
developed  between  the  ages  of  35  and  45,  rarely  during  adolescence 
and  early  adult  life  (between  the  ages  of  1 5  and  25).  Exophthalmic 
goitre,  on  the  contrary,  is  most  frequently  developed  between  the 
ages  of  15  and  35 — very  rarely  after  the  age  of  50.  In  my  series 
of  34  cases  of  adult  myxcedema,  the  average  age  at  which  the  dis- 
ease developed  in  women  was  41  years  and  in  men  43  years;  while 
in  my  series  of  76  cases  of  exophthalmic  goitre  (in  which  the  age  of 
onset  was  noted)  the  average  age  at  which  the  disease  developed  in 
the  female  cases  was  30  years,  and  in  the  male  cases  36  years. 

Myxcedema  is  most  frequent  in  married  women  who  have  borne 
children  or  have  had  large  families  ;  while  exophthalmic  goitre  is 
most  common  in  unmarried  (single)  women,  and  (?)  in  married 
women  who  have  not  borne  children  or  have  had  small  families. 
Pregnancy  seems,  as  a  rule,  to  exert  a  prejudicial  influence  on 
patients  who  are  affected  with  myxcedema  ;  while,  in  some  cases  of 
exophthalmic  goitre,  it  seems  to  prove  beneficial  or  even  curative. 
This  is  not,  however,  always  the  case  ;  in  two  of  my  cases  at  least 
pregnancy  seemed  to  aggravate  or  to  excite  the  development  of  the 
disease. 

In  my  series  of  29  cases  of  adult  myxcedema  in  females,  23  were 
married  and  6  were  single  ;  whereas  in  my  73  female  cases  of 
exophthalmic  goitre,  49  were  single  (when  the  disease  developed) 
and  24  married.  The  23  married  women  affected  with  myxcedema 
had, on  an  average,  5.1  children  each;  while  the  25  married  women 
affected  with  exophthalmic  goitre  had,  on  an  average,  3.2  children 
each.4- 

In  myxcedema,  the  temperature  is  subnormal,  unusually  stable, 
and  the  patients  are  extremely  susceptible  to  cold  ;  whereas  in 
exophthalmic  goitre,  temporary  elevations  of   temperature,  appa- 

*  A  few  cases  have  been  reported,  and  I  have  myself  met  with  two  instances, 
in  which  the  symptoms  of  myxcedema  were  developed  more  or  less  rapidly,  but 
in  some  of  these  cases  the  disease  had  probably  been  in  existence  for  some  time 
unknown  to  the  patient. 

t  This  difference  is  probably  in  part  at  least  (possibly  altogether)  accounted 
for  by  the  difference  in  age  ;  the  myxedematous  patients  were  older  and  had 
been  married  longer  than  the  exophthalmic  goitre  patients. 


EXOPHTHALMIC   GOITRE.  413 

rently  of  nervous  origin,  occasionally  occur,  the  temperature  equili- 
brium is  easily  disturbed,  and  the  patients  often  complain  of  a 
feeling  of  heat  and  flushing. 

In  myxcedema,  the  skin  is  extremely  dry  and  harsh  and  the 
secretion  of  sweat  abolished  or  greatly  diminished  ;  whereas  in 
exophthalmic  goitre,  the  skin  is  soft  and  moist,  and  excessive 
sweating  is,  in  the  great  majority  of  cases,  a  prominent  symptom. 

In  myxcedema,  the  electrical  resistance  of  the  skin  is  greatly 
increased,  whereas  in  exophthalmic  goitre  it  is  greatly  diminished. 

In  myxcedema,  the  bowels  are  usually  constipated  ;  whereas 
in  exophthalmic  goitre,  attacks  of  (nervous)  diarrhcea  are  apt  to 
occur. 

In  myxcedema,  placidity,  diminished  emotional  activity,  and 
slowness  of  all  nerve  processes,  are  conspicuous  features ;  whereas 
in  exophthalmic  goitre,  emotional  excitability,  irritability,  nervous 
instability  and  general  nervousness  are  always  very  marked. 

In  myxcedema.  the  administration  of  thyroid  extract  produces 
immediate  and  marked  improvement  ;  whereas  in  exophthalmic 
goitre,  if  I  may  judge  from  my  own  experience,  the  administration 
of  thyroid  extract  rarely  produces  any  improvement  and  in  fact 
in  many  cases  aggravates  the  symptoms  of  the  disease. 

It  must,  however,  be  stated  that  cases  have  been  reported  in 
which  the  symptoms  of  exophthalmic  goitre  have  improved  under 
the  administration  of  thyroid  extract.  This  is  directly  contrary  to 
my  own  experience  ;  and  it  must  be  remembered  that,  even  if  it 
does  occasionally  occur,  it  does  not  necessarily  prove  that  the 
symptoms  of  exophthalmic  goitre  (or  rather,  to  speak  more  cor- 
rectly, those  symptoms  of  exophthalmic  goitre  which  are  the  direct 
opposite  of  the  symptoms  of  myxcedema)  are  not  due  to  increased 
activity  of  the  thyroid  gland,  i.e.,  to  excessive  thyroidal  secretion. 
In  this  connection  it  is  important  to  remember  that  in  exophthalmic 
goitre  the  secretion  of  the  enlarged  thyroid  is  perhaps  abnormal  in 
character.  If  this  view  is  correct,  the  introduction  into  the  bodies 
of  healthy  persons  of  (normal)  thyroid  extract  will  not  be  likely  to 
produce  the  symptoms  of  exophthalmic  goitre.  If  the  thyroidal 
secretion  is  not  merely  increased  but  is  altered  in  character,  there 
is  no  difficulty  in  understanding  the  fact  that  in  some  cases  thyroid 
feeding  exerts  a  beneficial  influence  upon  the  symptoms  of  the 
disease. 

Further,  in  healthy  persons  the  prolonged  administration  of  thy- 
roid extract  may  produce  not  only  increased  frequency  of  the  heart's 
action  and  palpitation,  but  a  condition  of  general  nervousness  and 
tremor  which  resembles  very  closely,  and  is  perhaps  identical  with, 


414  DISEASES   OF   THE   BLOOD   GLANDS. 

the  nervousness  and  tremor  which  are  such  characteristic  symptoms 
of  exophthalmic  goitre. 

So  far  as  I  know,  prominence  of  the  eyeballs  (exophthalmos) 
has  only  once  been  noticed  after  thyroid  feeding ;  M.  Gagnevin, 
a  healthy  medical  student,  who  submitted  himself  from  the  15th  to 
the  23rd  of  March  to  full  doses  of  raw  thyroid  gland,  suffered  from 
palpitation,  increased  frequency  of  the  heart's  action,  tremors, 
sweatings,  flushings  and  exophthalmos,  "  sa  famille  s'apergoit  que 
les  yeux  lui  sortent  de  la  tete."  * 

I  am  fully  prepared  to  grant,  then,  that  many  of  the  symptoms 
of  exophthalmic  goitre  are  probably  the  result  of  an  increased  or 
perverted  action  of  the  thyroid  gland,  but  it  does  not  necessarily 
follow  that  the  enlargement  of  the  thyroid  is  the  primary  and 
fundamental  lesion.  It  is  possible  that  the  enlargement  of  the 
thyroid  gland  is  itself  the  result  of  a  primary  nervous  change. 

Taking  all  the  facts  into  consideration,  I  see  no  reason  to  alter 
the  opinion  expressed  in  my  article  on  exophthalmic  goitre  (Atlas 
of  Clinical  Medicine,  Vol.  ii.,  p.  99)  that  the  most  probable  view  of 
the  pathology  of  the  disease  which  it  is  possible  in  the  present  state 
of  our  knowledge  to  advance  is  : — 

First,  that  the  primary  cause  of  the  disease  is  a  lesion  or  rather 
perhaps  a  functional  disturbance  in  some  part  of  the  nervous  system, 
probably  some  part  of  the  medulla  oblongata. 

Second,  that  as  the  result  of  this  lesion  or  functional  nervous 
derangement,  the  thyroid  gland  becomes  enlarged  or  functionates 
in  an  abnormal  manner,  so  that  its  secretion  is  increased  and 
perhaps  altered  in  character. 

Third,  that  the  increased  or  perverted  secretion  of  the  enlarged 
thyroid  leads  to  the  production  of  a  widespread  disturbance  of 
function  in  the  nervous  and  other  tissues,  and  that  it  is  to  the 
secondary  disturbances  produced  in  this  way  that  many  of  the 
characteristic  symptoms  of  the  disease  are  due. 

Further  information  is  required  before  any  more  dogmatic  state- 
ment can  be  made. 

Although,  then,  in  the  present  position  of  our  knowledge  I  am 
disposed  to  think  that  the  primary  cause  of  the  disease  is  probably 
nervous,  1  am  by  no  means  prepared  to  deny  that  future  observa- 
tion may  perhaps  show  that  the  view  advanced  by  Mobius  and  sup- 
ported by  Greenfield,  viz.,  that  the  enlargement  of  the  thyroid  gland 
is  the  primary  and  fundamental  lesion,  is  correct. 

*  "  Le  Myxoudeme,"  par  lc  Dr  A.  Combe  dc  Lausanne,  p.  117. 


EXOPHTHALMIC   GOITRE.  415 


Diagnosis. 


In  typical  cases  the  diagnosis  of  exophthalmic  goitre  presents 
no  difficulty.  In  such  cases,  the  appearance  of  the  patient  is 
pathognomonic.  It  is  only  in  the  rudimentary  and  atypical  cases  in 
which  there  is  no  enlargement  of  the  thyroid  and  no  prominence 
of  the  eyeballs  that  any  real  difficulty  in  diagnosis  is  likely  to 
occur. 

The  Differential  Diagnosis  of  Ordinary  Goitre  and  of  Ex- 
ophthalmic Goitre. — In  ordinary  goitre,  the  enlargement  of  the 
thyroid  is  usually  greater  in  degree  and  firmer  in  consistency  than 
that  of  Graves'  disease.  In  ordinary  goitre,  pulsations  and  thrills 
are  not  usually  present  over  the  enlarged  gland.  While  the  in- 
creased frequency  of  the  heart's  action  (without  which  a  diagnosis 
of  exophthalmic  goitre  is  not  justified),  the  prominence  of  the  eye- 
balls, the  characteristic  general  nervousness  and  tremor  and  the 
numerous  secondary  symptoms,  some  of  which  are  almost  certain 
to  be  present  in  every  case  of  Graves'  disease,  are  not  observed,  01% 
perhaps,  to  speak  more  accurately,  are  only  accidentally  present. 
In  ordinary  goitre,  shortness  of  breath  and  other  symptoms  due  to 
the  pressure  of  the  enlarged  thyroid  upon  the  adjacent  organs  and 
parts  (sympathetic,  etc.)  may  be  developed  ;  these  pressure  symp- 
toms are  rarely  developed  in  exophthalmic  goitre,  at  all  events  in 
any  marked  degree. 

It  must,  however,  be  remembered  that  in  ordinary  goitre  when 
the  thyroid  is  very  much  enlarged,  the  nerves  (sympathetic  and 
vagus)  in  the  neck  may  be  pressed  upon  and  irritated.  It  is  said 
that  increased  frequency  of  the  heart's  action,  and  prominence  of 
the  eyeball  on  the  side  on  which  the  sympathetic  is  irritated,  may 
be  produced  in  this  manner.  In  cases  of  this  description,  a  satis- 
factory conclusion  as  to  the  true  nature  of  the  case  could  probably 
be  arrived  at  by  attention  to  the  following  points  : — The  large  size 
and  firm  consistency  of  the  enlarged  thyroid  ;  the  age  and  sex  of 
the  patient ;  the  history  of  the  case  ;  the  duration  of  the  disease  ; 
the  locality  in  which  the  patient  lived  (for  ordinary  goitre  is  apt  to 
be  endemic)  ;  the  fact  that  the  exophthalmos  would  probably  be 
unilateral  (for  it  is  not  likely  that  the  nerves — sympathetic  and 
vagus — on  both  sides  of  the  neck  would  be  pressed  upon  and  in- 
volved) ;  the  presence  of  other  distinctive  signs  of  irritation  of  the 
sympathetic  in  the  neck,  and  especially  dilatation  of  the  pupil 
and  unilateral  sweating  ;  together  with  the  absence  of  the  other 
secondary  symptoms,  some  of  which  are  almost  certain  to  be  present 
in  every  case  of  exophthalmic  goitre. 


416  DISEASES   OF   THE   BLOOD   GLANDS. 

The  Differential  Diagnosis  of  Exophthalmic  Goitre  and  of 
Simple  Functional  Palpitation. — Difficulty  in  distinguishing  these 
two  conditions  is  chiefly  apt  to  occur  in  atypical  cases  of  exoph- 
thalmic goitre  in  which  the  exophthalmos  and  enlargement  of  the 
thyroid  are  wanting.  In  Graves'  disease,  the  increased  frequency 
of  the  heart,  though  subject  to  paroxysmal  exacerbations,  is,  with 
rare  exceptions,  more  or  less  continuous  and  persistent ;  while  in 
functional  palpitation  and  hysterical  palpitation,  it  is  essentially 
paroxysmal  and  intermittent.  The  subjective  sensations  which  are 
associated  with  ordinary  functional  palpitation  are,  too,  as  a  rule, 
much  more  pronounced  than  those  associated  with  the  palpitation 
of  Graves'  disease. 

In  doubtful  cases,  the  presence  of  the  following  symptoms 
should  be  diligently  looked  for  : — General  nervousness  ;  the  charac- 
teristic tremor  :  flushings  and  sweating ;  nervous  diarrhoea ;  pig- 
mentation of  the  skin  ;  and  the  other  less  important  and  suggestive 
secondary  symptoms  of  exophthalmic  goitre. 

The  history  of  the  case,  the  exciting  cause  of  the  palpitation  and 
the  effects  of  treatment,  together  with  the  age  and  sex  of  the  patient, 
may  in  doubtful  cases  also  afford  corroborative  evidence  as  to  the 
true  nature  of  the  condition. 

The  Differential  Diagnosis  of  Organic  Disease  of  the  Heart 
and  of  Exophthalmic  Goitre. — Careful  consideration  of  the  his- 
tory and  whole  facts  of  the  case  will  in  the  great  majority  of  cases 
enable  a  competent  and  judicially-minded  observer  to  distinguish 
the  two  conditions  without  difficulty.  In  the  somewhat  excep- 
tional cases  in  which  Graves'  disease  is  complicated  with  organic 
disease  of  the  heart,  a  correct  diagnosis  can  only  of  course  be 
arrived  at  by  detecting  the  presence  or  absence  of  the  other  primary 
and  secondary  symptoms  which  are  characteristic  of  exophthalmic 
goitre. 

Prognosis. 

This  is  usually  a  matter  of  much  uncertainty.  In  most  cases, 
the  disease  runs  a  chronic  course,  lasting  for  months  or  years,  with 
perhaps  temporary  periods  of  improvement.  In  some  cases  (some 
authorities  state  a  third  or  fourth  of  the  whole,  but  according  to  my 
own  experience  this  is  too  high  an  estimate),  the  symptoms  after  a 
time  subside  and  a  complete  cure  is  ultimately  established.  In  a 
large  proportion  of  cases  in  which  improvement  occurs,  and  under 
this  head  I  would  include  the  great  majority  of  cases,  the  cure  is 
incomplete  ;  after  advancing  up  to  a  certain  point,  the  improvement 
seems  to  stop  and  the  symptoms,  or  some  of  them,  persist  in  a  less 


EXOPHTHALMIC   GOITRE.  417 

severe  form.  In  cases  of  this  description,  there  is  always  the  risk 
of  a  relapse.  In  some  rare  cases  in  which  the  disease  begins 
acutely,  the  symptoms  disappear  almost  as  rapidly  as  they  were 
established.  In  other  cases,  the  disease  steadily  progresses  from 
bad  to  worse  until  it  terminates  in  death. 

Probably,  in  the  future,  the  prognosis  will  be  more  hopeful  than 
it  has  been  in  the  past,  for  some  recent  methods  of  treatment 
(such,  for  example,  as  the  electrical  treatment,  excision  of  the  gland 
and  the  administration  of  phosphate  of  soda  and  thymus  extract) 
seem  to  be  attended  with  more  satisfactory  results  than  the  thera- 
peutic measures  which  were  formerly  employed. 

In  trying  to  form  an  opinion  as  to  the  probable  duration  and 
course  of  the  disease  in  any  particular  case,  the  following  are  the 
chief  circumstances  which  have  to  be  taken  into  account : — The  age 
and  sex  of  the  patient ;  the  rapidity  of  development  and  the  length 
of  time  which  the  disease  has  lasted  ;  the  degree  of  general  nervous- 
ness ;  the  rapidity  of  the  pulse  ;  the  severity  of  the  general  consti- 
tutional symptoms,  more  especially  the  presence  or  absence  of 
emaciation,  marasmus  and  cachexia  ;  the  effects  of  treatment ;  and 
the  presence  or  absence  of  complications. 

Other  things  being  equal,  the  fact  that  the  patient  is  middle- 
aged  or  old  is,  I  think,  unfavourable,  as  regards  the  duration  at  all 
events.  In  my  experience,  the  cases  which  occur  in  men  are 
usually  difficult  to  cure.  The  more  rapidly  the  disease  is  developed, 
in  a  severe  form,  the  worse  perhaps  the  prognosis  ;  but  I  speak  with 
great  reserve  on  this  point,  for  in  some  cases  in  which  the  symp- 
toms of  the  disease  are  suddenly  developed,  they  suddenly  subside. 
The  degree  of  the  exophthalmos  and  the  extent  of  the  enlarge- 
ment of  the  thyroid  do  not  seem  to  afford  any  true  criteria  as  to 
the  severity  of  the  case  and  the  length  of  time  which  the  disease  is 
likely  to  continue  ;  for  in  atypical  ("  fruste  ")  cases,  in  which  there 
is  no  goitre  and  no  exophthalmos,  the  disease  is  often  severe  and 
of  long  duration.  The  degree  of  general  nervousness  and  the  fre- 
quency of  the  pulse  are  more  certain  guides  to  the  prognosis. 
Other  things  being  equal,  the  greater  the  general  nervousness  and 
the  greater  the  frequency  of  the  pulse,  the  greater  the  severity  of 
the  case  ;  vice  versa,  diminution  of  the  pulse  frequency  and  of  the 
general  nervousness  are  usually  favourable  indications.  Pregnancy 
seems  in  some  cases  to  exert  a  favourable  influence  upon  the  course 
of  the  disease  ;  but  in  a  small  proportion  of  cases  the  disease  is 
developed  during  or  immediately  after  pregnancy.  Profound  debi- 
lity, marked  emaciation,  marasmus  and  cachexia,  severe  and  intract- 
able diarrhoea  or  vomiting,  are  unfavourable  indications.     Asystole, 

2  D 


41 8  DISEASES   OF   THE   BLOOD   GLANDS. 

considerable  oedema  of  the  feet,  bronchitis  and  oedema  of  the  lungs, 
which  are  usually  only  developed  towards  the  termination  of  bad 
cases,  are  still  more  unfavourable  indications. 

The  manner  in  which  the  disease  behaves  under  treatment  is  in 
Graves'  disease,  as  in  so  many  other  affections,  a  point  of  the  greatest 
prognostic  importance — and  is  so  obvious  that  it  need  not  be  further 
insisted  upon. 

The  presence  or  absence  of  complications  must  always,  of  course, 
be  taken  into  account.  It  is  unnecessary  to  go  into  details;  the 
exact  nature  of  the  complication  must  guide  the  opinion  in  each 
particular  case. 

Mode  of  Death. — In  most  cases  in  which  the  patient  dies  from 
the  disease  itself  and  not  from  some  intercurrent  complication  or 
associated  lesion,  the  death  is  more  or  less  gradual  ;  but  in  some 
cases  the  patients  die  suddenly.  In  one  of  my  cases  the  patient 
while  seated  at  dinner  suddenly  complained  of  severe  pain  in  the 
head,  became  hemiplegic  and  died  in  a  couple  of  hours  ;  in  this 
case  there  was,  so  far  as  I  could  judge,  no  organic  valvular  lesion. 
In  rare  cases,  the  patient  dies  still  more  suddenly  from  cardiac 
syncope. 

Treatment. 

The  indications  for  treatment  are  : — Firstly,  to  remove  all 
causes  of  peripheral  irritation,  excitement,  etc.  ;  secondly,  to  improve 
the  condition  of  the  general  health  ;  and  thirdly,  to  employ  such 
drug  remedies  and  other  measures  of  treatment  as  experience  has 
shown  to  be  useful  and  salutary. 

Persons  suffering  from  exophthalmic  goitre  should  be  instructed 
to  lead  routine  and  quiet  lives  :  everything  (such  as  bodily  exertion 
or  mental  excitement)  which  is  found  to  accelerate  the  action 
of  the  heart,  to  produce  palpitation,  and  to  increase  the  general 
nervousness,  should,  so  far  as  possible,  be  avoided.  In  aggravated 
cases,  and  probably  in  all  cases  during  the  early  stages  of  the 
disease,  the  patients  should  be  confined  to  bed,  or  at  any  rate  be 
made  to  spend  the  greater  part  of  their  time  in  the  recumbent 
position. 

The  diet  should  be  easily  digestible  and  nutritious.  All  articles 
of  diet  which  are  likely  to  produce  flatulence  or  gastro-intestinal 
irritation  should  be  prohibited.  Tea,  coffee,  tobacco,  and  alcohol 
should  be  either  prohibited  altogether  or  very  sparingly  indulged  in. 

A  climate  which  is  neither  too  cold  nor  too  warm  is  perhaps 
the  most  suitable.  A  long  sea  voyage,  provided  the  patient  is  a 
good  sailor,  would  probably,  in  some  cases,  be  beneficial.     Stiller, 


EXOPHTHALMIC   GOITRE.  419 

quoted  by  Sajous,  reports  a  remarkable  amelioration  of  the  symp- 
toms in  two  cases  of  exophthalmic  goitre  under  the  influence  of 
high  altitudes. 

All  causes  of  debility  should  if  possible  be  removed.  Any 
uterine  or  ovarian  derangement  which  may  be  present  should  be 
attended  to.  Any  cause  of  peripheral  irritation  which  is  present 
should,  if  possible,  be  removed. 

In  those  cases  in  which  there  is  much  anaemia,  arsenic,  or  arsenic 
and  iron,  should  be  administered.  The  effect  which  iron  produces 
•on  the  patient  should  be  carefully  watched,  for  some  observers  have 
stated  that  it  is  apt  to  disagree  and  aggravate  the  symptoms,  but  I 
am  satisfied  that  in  some  cases  iron  is  beneficial. 

Arsenic,  strychnine,  quinine,  the  mineral  acids,  by  improving  the 
tone  of  the  general  health  and  of  the  nervous  system  in  particular, 
are  undoubtedly  useful  in  some  cases  ;  but  so  far  as  my  experience 
enables  me  to  judge,  they  do  not  seem  to  exert  any  distinctly  cura- 
tive effect  upon  the  diseased  condition. 

Of  drug  remedies,  belladonna  is  one  of  the  most  reliable. 
I  believe  that  digitalis,  or  digitalis  combined  with  iron,  is  in  some 
cases  beneficial.  Some  writers  state  that  digitalis  is  contra- 
indicated  in  Graves'  disease,  but  in  most  of  the  cases  in  which  I 
have  prescribed  it,  I  have  failed  to  observe  any  prejudicial  effect. 
In  some  cases,  strophanthus  appears  to  be  useful.  Aconite  and  the 
sulphate  of  sparteine  have  also  been  recommended  ;  in  the  few 
cases  in  which  I  have  tried  these  remedies,  I  have  failed  to  observe 
any  beneficial  effect  from  their  use.  Ergot  of  rye,  sulphonal  and 
antipyrin  have  also  been  said  to  be  beneficial.  Phosphate  of  soda 
or  phosphate  of  potash  (ten  to  twenty  grains  three  times  daily) 
seems  in  some  cases  to  produce  distinct  benefit.  I  have  usually 
employed  phosphate  of  potash,  for  phosphate  of  soda  is  more  apt  to 
produce  diarrhoea.  In  several  of  my  cases,  extract  of  thymus  gland 
has  appeared  to  produce  decided  improvement.  I  usually  begin 
with  one  five-grain  tabloid  three  times  daily,  increasing  the  dose 
gradually  but  continuously,  and  carefully  observing  the  effects  of 
the  remedy  upon  the  pulse,  general  nervousness,  thyroid  enlarge- 
ment, etc.  The  experience  of  different  observers,  however,  differs 
with  regard  to  the  effects  of  this  remedy.  Dr  Hector  Mackenzie, 
for  example,  states  that  in  none  of  the  cases  in  which  he  employed 
the  remedy  (thymus  extract)  was  any  improvement  noted. 

Some  years  ago  Charcot  recommended  the  application  of  ice- 
bags  to  the  praecordia  ;  but  latterly  he  seemed  to  have  abandoned 
this  method  of  treatment  in  favour  of  electricity,  which  has  been 
specially    recommended   by    M.    Vigoroux,    and    which    has    also 


420  DISEASES   OF   THE   BLOOD   GLANDS. 

yielded  satisfactory  results  in  the  hands  of  other  physicians.  On 
the  whole  it  would  appear  that  the  electrical  plan  of  treatment  is 
one  of  the  most  satisfactory  which  has  yet  been  introduced. 
Vigoroux  and  Charcot  recommend  that  the  constant  current  should 
be  applied  to  the  neck,  and  the  interrupted  current  to  the  precordial 
region.  In  using  the  constant  current,  the  electrodes  should  be 
firmly  pressed  deep  into  the  neck,  beneath  the  angle  of  the  jaw  on 
each  side.  The  current  may  be  allowed  to  pass  from  five  to  seven 
minutes  at  each  sitting.  Care  must  be  taken  that  the  skin  is  not 
vesicated  under  the  negative  electrode.  A  current  which,  after  it 
has  been  allowed  to  pass  from  five  to  seven  minutes,  gently  reddens, 
but  which  does  not  vesicate,  the  skin  and  which  is  not  painful,  is, 
for  practical  purposes,  sufficient.  The  strength  of  the  faradic 
current  should  be  regulated  by  the  sensations  of  the  patient.  The 
strongest  interrupted  current  which  can  be  comfortably  borne  may 
be  employed.  In  employing  electricity  in  the  treatment  of  exoph- 
thalmic goitre,  it  is  well  to  remember  that  the  patients  are  highly 
nervous  and  very  easily  agitated  ;  it  is  therefore  advisable  to  com- 
mence with  weak  currents.  As  the  patient  becomes  accustomed  to 
the  treatment,  the  strength  of  current  may  be  gradually  increased. 

Excision  of  the  enlarged  gland  or  of  part  of  the  enlarged  gland 
seems  to  have  been  followed  by  remarkable  improvement  in  some 
cases  ;  but  it  remains  to  be  shown  whether  this  somewhat  serious 
surgical  procedure,  which  in  more  than  one  case  has  been  followed 
by  sudden  death,  is  advisable  in  any  considerable  number  of  cases. 
It  seems  to  me  that,  even  granting  that  the  results  which  Dr  Lemke 
and  some  other  surgeons  have  obtained  are  confirmed  by  subse- 
quent experience,  excision  of  the  gland  should  only  be  practised  in 
aggravated  cases  of  the  disease,  in  which  medical  and  electrical 
treatment  has  been  fairly  and  diligently  employed  for  a  considerable 
period  of  time  and  has  failed  to  give  relief;  or  in  those  cases  in 
which  the  pressure  of  the  enlarged  thyroid  on  the  trachea  is  attended 
with  dangerous  dyspnoea. 

Other  methods  of  surgical  procedure  have  also  recently  been 
recommended,  viz.,  ligature  of  the  thyroidal  vessels,  division  of  the 
isthmus  of  the  gland,  stripping  off  the  capsule  and  exposing  the 
gland  so  as  to  cause  it  to  atrophy,  division  of  the  cervical  sympa- 
thetic, and  complete  excision  of  the  whole  sympathetic  on  both 
sides  of  the  neck.  My  personal  experience  does  not  enable  me  to 
pronounce  an  opinion  upon  any  of  these  methods  of  treatment. 
Jonnesco  states  (Ccntralbl.  f.  Chir.,  Leipsig,  1897,  No.  2)  that  in  ten 
cases  in  which  he  excised  the  whole  sympathetic  on  both  sides  of 
the  neck,  complete  recovery  resulted  in  six  cases  and  marked  im- 
provement in  four  cases. 


ACROMEGALY. 

Historical  Note. — This  rare  disease,  to  which  the  synonyms 
megalacria,  pachyacria,  pachycemia,  and  Marie  s  disease,  have  also 
been  applied,  was  first  systematically  described  in  the  year  1885  by 
a  French  physician,  Dr  Pierre  Marie,  who  termed  it  acromegaly 
because  of  the  enlargement  of  the  extremities  (axpov=  extremity, 
and  /xeya?  =  great),  which  is  its  most  striking  feature. 

The  disease  is  not  a  new  one  ;  for,  as  Marie  has  himself  pointed 
out,  cases  which  were  without  doubt  typical  examples  of  acrome- 
galy had  been  met  with  before  the  year  1885.  Several  are  recorded 
in  medical  literature.  But  to  Marie  belongs  the  merit  of  being  the 
first  to  recognise  that  the  disease  is  a  distinct  clinical  entity  and  to 
give  a  systematic  description  of  its  peculiar  clinical  features. 

Etiology. 

Age. — In  the  great  majority  of  cases  which  have  been  recorded, 
the  disease  seems  to  have  commenced  between  the  ages  of  15  and 
40  ;  but  occasionally  the  onset  is  earlier  or  later  than  the  fifteenth 
and  fortieth  years  respectively.  In  the  cases  analysed  by  Hins- 
dale, the  age  at  onset  was  as  follows: — "0-10  years,  4  cases; 
11-20  years,  19  cases  ;  21-30  years,  33  cases  ;  31-40  years,  22  cases  ; 
41-50  years,  10  cases;  51-60  years,  2  cases;  61-70  years,  1  case; 
71  years,  1  case." 

Sex.— Acromegaly  seems  to  occur  with  equal  frequency  in  the 
two  sexes.  In  this  respect  it  contrasts  very  remarkably  with 
myxcedema,  with  which  perhaps  it  has  some  relationship,  and 
with  which  it  is  sometimes  confounded  ;  for  myxcedema,  as  has 
been  already  pointed  out,  is  very  much  more  common  in  women 
than  in  men. 

Race  and  Locality. — Acromegaly  is  said  to  occur  amongst  all 
races  and  in  all  parts  of  the  world  ;  but  there  are  some  grounds,  I 
think,  for  supposing  that  it  is  more  common  in  some  countries  and 
some  localities  than  in  others.  In  Scotland,  if  I  may  judge  from  my 
own  observation,  the   disease  is  extremely  rare  ;    whereas,  in  the 


422  DISEASES   OF   THE   BLOOD   GLANDS. 

neighbourhood  of  Heidelberg  it  appears  to  be  comparatively  speak- 
ing common. 

Heredity. — Acromegaly  appears  rarely  to  be  inherited,  though 
in  exceptional  instances  more  than  one  case  has  occurred  in  the 
same  family.  Virchow  mentions  a  case  in  which  two  brothers  were 
affected  ;  in  another  case  a  father  and  daughter  suffered  from  the 
disease. 

Exciting  or  Aggravating"  Causes. — Exposure  to  cold,  trau- 
matic injuries,  grief,  anxiety  and  other  causes  of  mental  depression 
or  excitement  have  preceded  the  onset  (or  rather  the  apparent 
onset)  in  some  cases  ;  but  it  is  exceedingly  doubtful  whether  these 
conditions,  traumatic  injuries  to  the  head  perhaps  in  some  cases 
excepted,  are  real  causes  of  the  disease.  They  are  probably  rather 
contributory  exciting  causes  which  aggravate  the  condition  and 
favour  its  more  rapid  development  in  the  early  stages. 

Mode  of  Onset,  Course  and  Duration. — The  onset  is  usually 
very  gradual  and  insidious.  In  many  cases,  the  disease  has  already 
been  in  existence  for  some  time  before  its  presence  is  suspected 
either  by  the  patient  or  the  doctor.  Occasionally,  the  onset  is  more 
rapid.  In  one  of  my  cases  (Case  I.),  the  characteristic  enlarge- 
ment of  the  hands  and  feet  and  the  marked  alteration  in  the  shape 
and  appearance  of  the  face  seem  to  have  developed,  in  a  sufficient 
degree  to  attract  attention,  within  the  comparatively  short  period  of 
three  months.  The  course  is  usually  very  slow  and  chronic,  but  in 
most  cases  progressive.  The  duration  is  usually  long ;  cases  may 
go  on  for  ten,  twenty,  thirty  years,  or  even  longer.  In  rare  cases, 
in  which  the  enlargement  of  the  pituitary  body  is  perhaps  not 
merely  simple  but  malignant  (sarcomatous  or  cancerous)  in  charac- 
ter, the  course  may  be  much  more  rapid. 

Clinical  History. 

The  most  striking  characteristic  feature  of  the  disease  is  an 
enlargement  of  the  extremities  of  the  body  ;  hence  the  term  acro- 
megaly. The  hands,  feet  and  the  "  cephalic  extremity  "  (as  French 
writers  term  the  face)  are  the  parts  which  are  chiefly  affected  ;  but 
other  parts  are  also  involved.  The  tongue,  for  example,  is  in  some 
cases  of  great  size,  and  the  sternum,  ribs  and  clavicles  are  often 
also  very  much  enlarged  ;  while,  in  fully  developed  cases,  the  trunk- 
presents  characteristic  alterations. 

The  enlargement  is,  in  the  great  majority  of  cases,  due  to  an 
increase  of  all  the  tissues  composing  the  affected  parts — the  bones 
as  well  as  the  soft  tissues  ;  though  in  rare  cases  the  bones  of  the 


ACROMEGALY.  423 

hands  and  feet  do  not  appear  to  be  enlarged.*  The  enlargement  is 
not  due  to  oedema  ;  there  is  no  pitting  on  pressure.  The  palms 
and  soles,  in  which  the  enlargement  of  the  soft  tissues  is  most 
noticeable,  feel  firm  and  elastic  as  if  cushioned  with  a  thick  layer  of 
firm  elastic  tissue  and  fat. 

Let  me  now  describe  the  condition  of  the  individual  parts  in 
more  detail. 

The  upper  extremities. — The  hands  and  fingers  are  greatly 
enlarged,  particularly  in  breadth.  The  hands  are,  in  most  cases, 
enormously  broad  ;  they  have  been  termed  "  spade-shaped,"  "  battle- 
dore-shaped," "  paw-shaped,"  etc.  The  increase  of  the  soft  tissues 
is  usually  well  seen  in  the  palms,  which  appear  to  be  thickly  padded 
with  fat.  The  creases  in  the  palms  and  soles  and  the  interphalan- 
geal  folds  on  the  upper  surface  of  the  fingers  are  usually  deeper  than 
normal.  The  fingers  are  usually  very  broad  and  somewhat  fiat ; 
they  have  been  termed  sausage-shaped.  Though  nodosities  are 
sometimes  present  on  the  phalanges,  giving  the  hand  and  fingers 
a  rugged  appearance,  the  enlargement  of  the  fingers  is,  as  a  rule,, 
uniform  ;  there  is  very  little  if  any  tapering  off  at  the  extremities  ; 
and  it  should  be  particularly  noted  that  there  is  no  clubbing  of  the 
finger  tips.  In  this  respect  acromegaly  differs  from  the  condition 
to  which  P.  Marie  has  given  the  term  hypertrophic  pulmonary  osteo- 
arthropathy. 

The  nails  usually  appear  small  in  proportion  to  the  size  of  the 
fingers ;  they  are  usually  broad,  flattened  out  transversely,  and  in 
many  cases  grooved  in  the  longitudinal  direction. 

The  wrist  joints  are  not  as  a  rule  markedly  affected,  though  in 
some  cases  they  are  moderately  enlarged. 

The  lower  extremities. — The  lower  extremities  are  affected  in 
the  same  way  as  the  upper.  The  feet  are  very  much  enlarged  and 
the  increase  is  chiefly  in  breadth.  The  toes,  particularly  the  great 
toe,  are  often  much  enlarged,  flattened  and  square  at  the  end.  The 
nails  of  the  toes  are  square  and  in  some  cases  grooved  ;  in  others, 
buried,  as  it  were,  by  the  great  increase  of  the  soft  parts. 

The  ankles,  like  the  wrists,  may  be  enlarged,  but  in  most  cases 
they  are  not  affected,  at  all  events  in  any  marked  degree. 

The  head  and  face. — The  face  usually  undergoes  a  notable 
alteration  in  shape  as  the  disease  advances  ;  it  becomes  lengthened, 
especially  below  the  forehead,  and  assumes  an  elongated  oval 
shape.       In    most  cases,    the   expression    is    somewhat    sad,    heavy 

*  Sir  William  Broadbent  has  recently  reported  a  case  of  this  kind,  "  Lancet," 
Vol.  i.,  1896,  p.  846. 


424  DISEASES   OF   THE    BLOOD   GLANDS. 

and  apathetic.  In  typical  and  well-marked  cases  of  the  disease, 
the  forehead  looks  low  in  proportion  to  the  rest  of  the  face ;  the 
nose  becomes  thickened,  flattened  and  increased  in  size,  and  this 
increase  is  due  to  an  enlargement  of  all  the  tissues  which  enter  into 
its  composition — the  bones,  cartilages  and  soft  parts  all  being  in- 
volved ;  the  cheek  bones  are  prominent ;  the  lips,  especially  the  lower 
lip,  are  thick  ;  in  many  cases  the  lower  lip  hangs  down  and  is 
everted  ;  the  superciliary  ridges  are  in  some  cases  markedly  en- 
larged ;  the  eyes  are  set  wide  apart  ;  in  some  cases  they  appear  to 
be,  relatively  to  the  large  face,  unduly  small  and  more  prominent 
than  normal  ;  the  orbital  and  temporal  ridges  may  become  thick 
and  prominent.  In  some  cases  the  eyebrozus  are  thick.  The  upper 
lid  sometimes  has  a  full  swollen  appearance  ;  the  lower  edge  is  in 
many  cases  increased  in  size.  The  lower  jaw  is  usually  markedly 
enlarged ;  this  is  one  of  the  most  constant  and  characteristic 
changes.  The  chin  usually  projects  forwards  ;  the  angle  of  the 
jaw  is  less  acute  than  normal.  In  some  cases,  the  alveolar  process 
in  both  jaws  is  considerably  thickened  ;  in  others,  it  is  more  or  less 
atrophied  in  consequence  of  the  falling  out  of  the  teeth.  Owing  to 
the  increased  size  and  width  of  the  lower  jaw,  the  front  teeth  are  set 
widely  apart ;  in  many  cases  they  are  separated  from  one  another 
by  considerable  spaces  which  did  not  exist  before  the  disease  com- 
menced. The  palate  is  in  many  cases  not  only  high  but  very 
broad,  the  space  at  the  roof  of  the  mouth  being  very  capacious. 
As  has  been  previously  stated,  the  tongue  is  in  some  cases  markedly 
enlarged. 

The  neck  is  usually  short  and  thick  and  the  larynx  large  and 
prominent. 

The  voice  is  generally  low  toned,  rough,  and  harsh. 

In  some  cases  the  thyroid  gland  is  of  normal  size ;  in  others 
atrophied  ;  in  others  hypertrophied. 

The  long  bones  are  not  usually  affected,  except  in  the  "giant  form" 
of  the  disease. 

The  trunk — .In  the  advanced  stages  of  the  disease  the  trunk 
presents  marked  and  characteristic  changes.  The  sternum,  clavicles 
and  ribs  are  enlarged,  the  manubrium  sterni  being  increased  in 
length  and  breadth,  and  probably  also  in  thickness.  In  many  cases, 
as  Professor  Erb  has  shown,  a  pyramidal  area  of  dulness  can  be 
demonstrated  on  percussion  over  the  upper  part  of  the  bone ;  in 
some  cases,  it  appears  to  be  due  to  the  presence  of  a  persistent  and 
enlarged  thymus  gland  ;  in  others,  to  the  increased  thickness  of 
the  bone. 

As  the  disease  progresses,  the  thorax  becomes  enlarged  ;  it  is 


ACROMEGALY.  425 

usually  somewhat  flattened  from  side  to  side  ;  the  antero-posterior 
diameter  is  to  some  extent  increased,  and  the  chest  seems  to  project 
forwards. 

The  ribs  are  not  only  increased  in  thickness,  but  in  some  cases 
they  are  notably  enlarged  in  all  directions  and  elongated. 

The  vertebra  may  be  markedly  enlarged,  and  the  thickening  and 
enlargement  of  the  spinous  processes  can  in  some  cases  be  made  out 
during  life. 

The  pelvis  is  not  always  affected  in  any  marked  degree,  though 
in  some  cases  it  is  unusually  broad,  the  pelvic  bones  being  notably 
enlarged  ;  the  iliac  crests  and  spinous  processes  are  in  some  cases 
thickened. 

The  attitude  in  the  erect  position. — When  the  patient  stands 
in  the  erect  position,  the  shoulders  are  seen  to  be  rounded  ;  the  head 
is  usually  bent  forwards  towards  the  chest ;  in  some  cases  it  can 
only  be  held  erect  with  difficulty.  The  dorso-cervical  portion  of  the 
spine  is  in  many  cases  much  curved  (cervico-dorsal  kyphosis),  and 
there  is  sometimes  a  compensatory  lordosis  in  the  lumbar  region. 
In  consequence  of  the  development  of  these  changes  in  the  spinal 
column,  the  patient  shrinks  in  height  as  the  disease  advances.  As 
Dr  Hinsdale  states:  "The  peculiar  deformity  due  to  kyphosis, 
taken  in  connection  with  the  enormous  hands  and  feet,  may  give  an 
ape-like  appearance  to  the  subject."  * 

Changes  in  the  long  bones,  joints,  and  muscles. — It  must  be 
noted  that  the  alterations  in  the  bony  skeleton  which  constitute 
such  striking  and  characteristic  features  of  acromegaly  are  for  the 
most  part  confined  to  the  short  bones.  In  many  cases  the  long 
bones  seem  to  undergo  comparatively  little  change. 

In  some  cases  the  joints,  more  particularly  the  knees,  are 
enlarged  ;  but  the  articular  surfaces  of  the  bones  are  usually  quite 
normal.     In  some  cases  the  joints  creak  on  movement. 

The  muscles  are  usually  soft  and  flabby.  In  typical  and  fully 
developed  cases  of  the  disease,  muscular  weakness  and  debility  are 
highly  characteristic  symptoms  ;  but  in  the  earlier  stages  of  some 
cases,  the  muscles  are  hypertrophied  and  the  muscular  power  very 
great. 

Complaints. — Patients  affected  with  acromegaly  usually  com- 
plain of  "  weakness,"  "  debility,"  "  loss  of  muscular  power,"  "  loss  of 
strength,"  etc.  In  many  cases,  headache  is  a  prominent  symptom  ; 
in  others,  pains,  which  are  often  described  as  rheumatic  or  neuralgic 
in  character,   are  complained    of   in    the  bones    and    muscles.     In 

*  "Acromegaly,"  by  Guy  Hinsdale,  M.A.,  M.D.,  p.  n. 


426  DISEASES   OF   THE   BLOOD   GLANDS. 

almost  all  of  the  cases  which  have  been  reported,  an  excessive 
tendency  to  sweat  on  exertion  has  been  noted.  In  many  cases,  there 
is  dimness  of  vision,  or  rather  a  peculiar  defect  of  vision  (bilateral 
temporal  hemianopsia)  to  which  I  will  presently  refer  in  more  detail. 

The  condition  of  the  skin  and  its  appendages. — I  have 
already  stated  that  an  increased  tendency  to  sweat  is  a  characteristic 
feature  of  most  cases  of  acromegaly  ;  it  seems  to  be  due  to  a 
vasomotor  alteration.  In  some  cases,  the  hands  feel  cold,  moist  and 
clammy  to  the  touch  ;  they  sometimes  become  dead  and  blanched. 
Owing  to  its  moist  condition,  the  electrical  resistance  of  the  skin 
may  be  somewhat  diminished — a  fact  which  was  pointed  out  by 
Erb,  who  also  states  that  the  electrical  excitability  of  the  muscles 
is  increased. 

In  many  of  the  cases  of  acromegaly  which  have  been  recorded, 
numerous  small  stalked  warts  were  developed  on  the  surface  of  the 
body  ;  they  are  probably  the  result  of  the  vasomotor  and  nutritive 
alterations  in  the  skin.  The  term  "  molluscum  fibrosum  "  has  been 
applied  to  them,  but  in  those  cases  which  have  come  under  my  own 
notice  the  little  cutaneous  outgrowths  appeared  to  be  true  warts, 
and  not  molluscous  tumours.  The  warty  nature  was  demonstrated 
in  one  of  my  cases  by  Dr  Gulland,  who  kindly  removed  one  of  the 
little  outgrowths,  and  made  microscopical  sections  of  it.  In 
reference  to  this  point  Souza-Leite  says  : — "  A  certain  number  of 
patients  present  on  the  upper  part  of  the  body,  especially  on  the 
upper  part  of  the  trunk,  little  cutaneous  tumours,  sometimes 
pedunculated.  They  are  the  size  of  a  millet  or  hemp  seed,  or  even 
larger.  They  are  of  a  red  colour,  sometimes  violet,  and  very 
numerous.  The  condition  presented  is  that  of  molluscum  fibrosum 
or  pendulum.  A  patient  of  Verstraeten  presented  numerous  flat 
warts  round  the  neck  and  waist.  At  first  Marie  was  inclined  to 
regard  molluscum  as  a  simple  coincidence  of  acromegaly,  but  having 
since  found  it  in  all  his  patients  he  questions  if  it  is  not  one  of  the 
phenomena  of  acromegaly,  due  to  changes  in  the  nutrition  of  the 
skin."  * 

In  some  cases,  the  skin  of  the  face,  more  especially  about  the 
eyelids,  and  of  the  nose,  and  it  may  be  of  other  parts  of  the  body, 
is  more  deeply  pigmented  than  normal.  In  many  cases  it  is  of  a 
dingy,  dirt)',  sallow  hue,  often  coarse  in  texture,  and  in  some  cases 
thickly  studded  with  sebaceous  points.  The  scalp  is  in  some  cases 
thickened  and  hypertrophied. 

*  "Acromegaly":     Pierre    Marie    and    Souza-Leite.      Sydenham    Society's 
Translation,  p.  54. 


ACROMEGALY.  427 

The  hair  of  the  scalp  is  usually  abundant  and  thick,  coarse  and 
wiry  ;  the  hairs  of  the  body  and  pubis  are  usually  strong,  probably 
thicker  than  normal  but  not  more  numerous  ;  in  women  the  little 
hairs  round  the  nipple  and  between  the  breasts  are  in  some  cases 
larger  and  longer  than  normal. 

The  condition  of  the  nervous  system. — The  skin  sensibility 
rarely  presents  any  characteristic  alterations. 

The  reflexes,  both  superficial  and  deep,  are  usually  normal ;  but 
in  some  cases  the  knee-jerks  are  markedly  diminished  or  even 
abolished.  The  functions  of  the  bladder  and  rectum  are  rarely,  if 
ever,  affected. 

The  condition  of  the  special  senses. — In  a  considerable  number  of 
the  cases  of  acromegaly  which  have  been  recorded,  bilateral 
temporal  hemianopsia  was  present.  From  a  diagnostic  point  of 
view,  this  is  a  very  important  symptom,  and  is  due  to  the  pressure 
of  the  enlarged  pituitary  body  upon  the  optic  chiasma.  In  some 
cases,  the  optic  nerves  are  atrophied  ;  in  others  (but  this  is  quite 
exceptional)  there  is  double  optic  neuritis.  In  those  cases  in  which 
optic  atrophy  is  developed,  the  defect  of  vision  may  ultimately 
involve  the  nasal  as  well  as  the  temporal  half  of  the  fields  of  vision 
in  one  or  both  eyes,  complete  blindness  being  finally  produced. 

In  many  cases  of  acromegaly  headache  is  a  prominent  symptom, 
and  in  some  cases  vomiting  and  giddiness  are  also  present. 

The  hearing  is  occasionally  impaired,  but  this  is  exceptional. 
Tinnitus  aurium  and  noises  in  the  ears  are  in  many  cases  complained 
of;  but  it  is  doubtful  if  these  conditions,  which  are  so  common  in 
anaemia,  are  of  any  great  importance. 

Smell  is  rarely,  and  taste  very  rarely,  if  ever,  affected. 

Now,  headache,  vomiting,  and  giddiness,  when  associated  with 
optic  atrophy,  are  highly  suggestive  of  the  presence  of  an  intracranial 
tumour. 

Further,  when  temporal  hemianopsia — a  very  definite  localising 
symptom — is  present  in  addition  to  these  general  and  non-localising 
symptoms  (headache,  vomiting,  and  giddiness),  the  diagnosis  of  a 
coarse  lesion  (usually  a  tumour  of  the  pituitary  body  or  a  tumour  or 
aneurism  at  the  base  of  the  brain  which  is  pressing  on  the  central 
fibres  of  the  optic  chiasma)  is  warranted. 

The  headache,  which  is  such  a  common  symptom  in  acromegaly, 
has  been  described  as  one  of  the  fundamental  symptoms  of  the 
disease  ;  but  I  am  disposed  to  think  that  it  is  more  probably  a 
secondary  symptom,  due  to  the  presence  of  the  enlarged  pituitary 
body  within  the  skull.  What  I  mean  to  suggest  is,  that  the 
headache,    vomiting,    giddiness,    temporal    hemianopsia    and    optic 


428  DISEASES   OF   THE   BLOOD   GLANDS. 

atrophy  or  optic  neuritis  are  due  to  the  pressure  or  irritation 
produced  by  the  pituitary  tumour,  and  that  they  should  not  be 
placed  in  the  same  category  with  (i.e.,  that  they  have  not  the  same 
pathological  significance  as)  the  enlargement  of  the  extremities,  the 
increase  of  the  soft  parts  and  some  of  the  other  symptoms,  which 
are,  so  far  as  our  present  knowledge  enables  us  to  judge,  probably 
due  to  derangement  of  the  function  of  the  pituitary  gland,  and 
which  should  therefore  be  regarded  as  primary  and  fundamental 
symptoms  of  the  disease. 

The  mental  condition. — In  most  cases  of  acromegaly,  the  mental 
faculties  do  not  present  any  alterations  of  importance,  at  all  events 
during  the  earlier  stages  of  the  disease.  In  some  cases,  an  excessive 
tendency  to  sleep,  drowsiness,  and  symptoms  indicative  of  mental 
depression  or  melancholia  have  been  noted  ;  but  these  symptoms 
are  probably  in  no  way  peculiar  or  characteristic  ;  they  are  probably 
due  to  the  disturbance  of  the  cerebral  functions  produced  by  the 
presence  of  a  cerebral  tumour  (the  enlargement  of  the  pituitary),  or 
to  the  mental  dejection  and  depression  which  the  patients  experience 
in  consequence  of  the  loss  of  sight  and  the  progressive  and  incurable 
character  of  the  disease. 

The  condition  of  the  urine. —  In  many  cases  of  acromegaly, 
the  urine  is  notably  altered.  It  is  usually  increased  in  amount,  not 
infrequently  contains  sugar,  occasionally  peptone,  or  an  excess  of 
phosphates,  rarely  serum  albumen.  In  rare  cases,  the  amount  of 
urine  is  less  than  the  normal.  It  is  probable  I  think  that  these 
conditions  (polyuria,  glycosuria,  peptonuria,  etc.)  are,  like  the 
headache  and  vomiting,  not  primary  and  fundamental  but  merely 
secondary  symptoms,  due  to  the  pressure  of  the  enlarged  pituitary 
body  upon  the  surrounding  nervous  tissues.  It  is  well  known  that 
temporary  glycosuria  and  peptonuria  are  sometimes  met  with  in 
cases  of  intracranial  tumour,  and  especially  in  those  cases  in  which 
the  tumour  is  situated  in  the  neighbourhood  of  the  pituitary  body 
or  the  floor  of  the  fourth  ventricle.  Possibly,  however,  these  urinary 
alterations  are  fundamental  and  primary — part  and  parcel  of  a 
widespread  vasomotor  disturbance  which  is  the  direct  result  of  the 
disease,  i.e.,  of  the  derangement  of  the  functions  of  the  pituitary 
gland. 

The  condition  of  the  organs  of  circulation. — In  some  cases, 
the  heart  is  enlarged  and  the  superficial  arteries  atheromatous  ;  in 
some  cases,  the  cardiac  enlargement  seems  to  be  a  simple  hyper- 
trophy, in  others,  the  result  of  fibrosis  and  myocarditis.  Piles  and 
varicose  enlargement  of  the  veins  of  the  leg  are  not  unfrequently 
present.     The  pulse  is  often  quicker  than  normal. 


ACROMEGALY.  429 

The  condition  of  the  digestive  apparatus. — The  digestive 
organs  are  as  a  rule  normal.  In  some  of  the  recorded  cases,  the 
stomach  was  dilated  and  the  appetite  inordinately  large,  but  whether 
the  latter  symptom  has  any  real  significance  I  am  unable  to  say. 
Excessive  thirst  is,  too,  in  some  cases  a  prominent  symptom,  and  is 
perhaps  the  result  of  the  polyuria  and  glycosuria  above  described. 

The  general  state  of  nutrition. — Since  the  most  characteristic 
feature  of  acromegaly  is  an  increase  not  only  of  the  bones  but  also 
of  the  soft  parts,  it  is  unnecessary  to  say  that,  in  the  early  stages  at 
all  events,  patients  affected  with  the  disease  appear  to  be  well 
nourished. 

The  condition  of  the  blood. — This  does  not,  so  far  as  I  know, 
present  any  characteristic  changes,  though  a  certain  degree  of 
anaemia  is  sometimes  present. 

The  condition  of  the  ductless  glands. — In  many  of  the  typical 
cases  of  acromegaly  which  have  been  examined  post  mortem,  the 
pituitary  gland  has  been  much  enlarged.  During  life  the  existence 
of  this  enlargement  is  in  many  cases  proved  by  the  presence  of 
bilateral  temporal  hemianopsia.  In  some  cases,  the  thyroid  gla?id 
is  also  enlarged  ;  in  others  (and  this  is  perhaps  more  common), 
atrophied.  In  some  cases,  the  thymus  gland  not  only  persists  but 
is  notably  enlarged.  In  some  cases,  the  pineal  gland  has  been 
found  enlarged  after  death,  but  so  far  as  I  know  this  enlargement 
is  not  attended  with  any  distinct  symptoms  during  life.  In  one  of 
the  recorded  cases  the  lymphatic  glands  beneath  the  jaws  were  very 
much  enlarged. 

The  condition  of  the  sexual  organs. — In  females  affected  with 
the  disease,  amenorrhcea  is  almost  always  present,  and  is  in  many 
cases  the  first  symptom  to  attract  attention.  The  ovaries  and 
uterus  are  usually  atrophied.  The  mammae  are  in  some  cases 
atrophied,  but  the  nipples  are  usually  of  large  size  and  often 
surrounded  by  an  increased  growth  of  coarse  hair.  The  external 
genitals  (labia  majora,  nymphae  and  especially  the  clitoris)  are  in 
some  cases  enlarged.  In  men,  the  penis  is  sometimes  increased  in 
size  ;  the  testicles  are  in  some  cases  enlarged,  but  more  frequently 
atrophied.  There  is  usually  complete  loss  of  sexual  desire  and 
virile  power. 

Summary  of  the  chief  symptoms. — To  sum  up,  the  chief 
characteristics  of  this  remarkable  disease  are  : — 

(1)  An  enlargement  or  overgrowth  of  the  extremities  (hands,  feet 
and  face),  and  (though  this  is  less  evident)  of  the  ribs,  sternum,  ver- 
tebrae, iliac  bones,  and  in  fact  of  all  the  bony  structures  of  the  body  ; 
it  must  be  remembered  that  the  overgrowth  is  not  confined  to  the 


430  DISEASES   OF   THE    BLOOD   GLANDS. 

osseous  structures,  for  the  soft  parts — notably  the  soft  tissues  of  the 
palms  and  soles,  the  tongue,  and  in  some  cases  the  clitoris  and 
penis — are  also  involved  ;  (2)  gradually  increasing  weakness  ;  (3)  a 
tendency  to  excessive  sweating,  especially  on  exertion  ;  (4)  in 
women,  arrested  menstruation  which  often  occurs  at  an  early  stage 
of  the  disease  ;  and  in  men,  loss  of  sexual  desire  and  impotence, 
conditions  which  are  usually  developed  in  the  later  stages  ;  (5) 
vasomotor  disturbances  (a  "  dead  "  condition  of  the  fingers,  &c.) ; 
(6)  the  development  on  the  surface  of  the  body  of  little  warty 
tumours;  (7)  an  increased  growth  of  hair  ;  (8)  neuralgic  and  myalgic 
pains  ;  (9)  atrophy  of  the  mammary  glands  and  ovaries,  and  in 
some  cases  of  the  testicles  ;  (10)  headache,  with  which  vomiting 
and  vertigo  are  sometimes  associated;  (11)  bilateral  temporal 
hemianopsia  and  it  may  be  optic  atrophy  or  (but  this  is  rare)  optic 
neuritis;  (12)  glycosuria,  polyuria  and  peptonuria;  (13)  inordinate 
appetite  and  thirst;  (14)  mental  depression,  stupor,  and  less 
frequently  maniacal  excitement,  &c. 

As  I  have  previously  stated,  it  is  doubtful  whether  all  of  these 
symptoms  should  be  placed  in  the  same  pathological  category  or 
not.  It  is  possible  that  some  of  them,  such  as  the  enlargement  of 
the  extremities,  the  debility,  the  excessive  sweating,  are  primary, 
i.e.,  the  direct  result  of  a  derangement  of  the  function  of  the  pituitary 
gland  ;  and  that  others,  such  as  headache,  bilateral  temporal 
hemianopsia,  polyuria,  etc.,  are  secondary,  i.e.,  the  indirect  result  of, 
and  due  to,  the  increased  size  of  the  pituitary  body  and  to  the 
derangement  of  the  cerebral  functions  which  the  tumour  (the 
enlarged  pituitary  body)  produces. 

Varieties. — Two  forms  or  varieties  of  acromegaly  have  been 
described,  viz.,  (1)  the  massive  type,  and  (2)  the  giant  or  long  type 
of  the  disease  ;  for  it  has  been  shown  that  in  some  giants  the 
pituitary  body  is  enlarged  and  the  symptoms,  or  some  of  the 
symptoms,  of  acromegaly  are  present.  With  regard  to  this  point 
Hinsdale  says: — "As  to  the  two  types  of  acromegaly,  there  is  a 
disposition  to  assume  the  long  or  giant  type  of  acromegaly,  if  the 
disease  originated  in  the  period  of  adolescence  ;  but  if  the  onset  is 
delayed  until  later  life,  the  type  will  be  large  (Brissaud  and 
Meige)."  * 

Dr  Hinsdale  throws  out  the  suggestion  that  there  is  perhaps  a 
relationship,  in  some  cases  at  all  events,  between  giantism  and 
dwarfism.  On  this  point  he  says  : — "  Cases  have  arisen  which  have 
suggested   that   there   is,   paradoxical    as  it    may   seem,   a   relation 

*  "Acromegaly,"  by  Guy  Hinsdale,  A.M.,  M.D.,  p.  51. 


ACROMEGALY.  43 1 

between  giantism  and  dwarfism.  Such  cases  are  those  described 
by  Mr  Jonathan  Hutchinson  in  1866  and  by  Mr  H.  Gilford  in  1896. 
In  the  latter  case,  while  the  patient  was  clearly  a  dwarf,  there  were 
parts  that  were  more  than  fully  developed  ;  and  Mr  Gilford  was 
led  by  this  case  to  the  study  of  dwarfism  and  giantism.  He  sees 
a  close  relationship  between  these  deviations  in  nutrition,  and 
suggests  the  term  micromegaly  as  descriptive  of  his  case  and  others 
allied  to  it.  He  thinks  it  not  impossible  that  the  cause  of  acro- 
megaly operating  before  birth  may  bring  about  micromegaly  ;  for 
many  giants  have  evidently  owed  their  proportions  to  the  former. 
May  the  one  be  the  congenital  condition  of  the  other,  or  are  the 
two  opposite  states  ?  "  * 

Morbid  Anatomy  and  Pathology. 

In  addition  to  the  enlargement  of  the  bony  structures  which 
is  such  a  striking  feature  of  almost  every  case  of  acromegaly  (but 
which  is  evidently  a  result  of  the  primary  lesion,  whatever  it  may 
be,  which  is  the  cause  of  the  disease),  the  most  constant  and 
noticeable  pathological  change  found  after  death  is  enlargement 
of  the  pituitary  body.  The  gland  is  usually  so  much  increased  in 
size  that  the  sella  turcica  (the  bony  bed  in  which  it  is  embedded) 
is  greatly  enlarged. 

In  some  cases,  morbid  changes  have  also  been  found  in  the 
sympathetic,  in  the  peripheral  nerves  and  in  the  spinal  cord.  In 
some  cases,  the  heart,  arteries,  and  some  of  the  abdominal  and 
thoracic  viscera  have  also  been  found  affected  (enlarged,  sclerosed, 
etc.),  after  death.  Further,  as  has  been  already  stated  in  connection 
with  the  clinical  history,  the  ductless  glands,  other  than  the  pituitary 
gland,  are  in  some  cases  affected  ;  though  the  thyroid  gland  is  in 
some  cases  normal,  in  other  cases  it  is  enlarged,  in  others  again 
atrophied  ;  the  thymus  gland  in  some  cases  persists  and  may  be 
considerably  enlarged  ;  in  one  case  at  least,  the  pineal  gland  was 
increased  in  size. 

The  exact  significance  of  many  of  these  morbid  changes  is  at 
present  doubtful  ;  but  the  weight  of  evidence  seems  strongly  in 
favour  of  the  view  that  the  enlargement  of  the  pituitary  body  is  the 
primary  and  fundamental  lesion  of  the  disease.  According  to  this 
view,  the  pituitary,  like  the  thyroid,  is  a  blood  gland,  which  is,  in 
some  way  or  another,  actively  concerned  in  the  regulation  of  the 
nutrition    and    metabolism    of  the    body,    and    perhaps    especially 

*  "Acromegaly,"  by  Guy  Hinsdale,  A.M.,  M.D.,  p.  51. 


432  DISEASES   OF   THE   BLOOD   GLANDS. 

concerned  in  the  regulation  of  the  nutrition  and  metabolism  of  the 
nervous  tissues. 

Another  view,  which  seems,  however,  much  less  likely,  is  that 
acromegaly  is  the  result  of  nervous  changes — a  trophic  neurosis — 
and  that  the  enlargement  of  the  pituitary  body  is  merely  part  and 
parcel  of  the  trophic  (or,  perhaps,  to  speak  more  correctly,  of  the 
hypertrophic)  change  which  affects  many  of  the  tissues  and  organs 
of  the  body.  Further,  it  has  been  supposed  that  the  enlargement 
of  the  pituitary  body  which  is  primarily  the  result  of  a  nervous 
change,  produces  in  its  turn  (by  the  disturbance — diminution, 
increase,  or  perversion — of  its  internal  secretion)  nutritional  changes 
in  the  tissues  and  organs  of  the  body. 

The  exact  manner  in  which  the  lesion  of  the  pituitary  body 
produces  the  symptoms  of  the  disease  has  not,  however,  as  yet  been 
definitely  determined.  It  has  been  suggested  that  the  disease 
(acromegaly)  is  due  to  : — (i)  arrested,  (2)  increased,  or  (3)  perverted 
pituitary  secretion. 

If  the  enlargement  of  the  pituitary  body  is  a  true  hypertrophy, 
the  view  which  supposes  that  the  symptoms  of  acromegaly  are  due 
to  an  increased  or  perverted  action  of  the  pituitary  gland  is  very 
plausible.  The  pituitary  body  closely  resembles  in  structure  the 
thyroid  gland,  but  our  knowledge  of  the  function  of  the  pituitary 
body  is  as  yet  altogether  indefinite.  It  is  possible  that  the  study  of 
acromegaly  may  throw  some  light  on  this  obscure  physiological 
problem,  just  as  the  study  of  myxcedema  has  thrown  so  much  light 
on  the  function  of  the  thyroid  gland.  The  remarkable  influence 
which  the  thyroid  gland  undoubtedly  exerts  upon  the  nutrition  of 
the  body  suggests  that  the  pituitary  and  other  ductless  glands  may, 
like  the  thyroid,  exert  a  powerful  influence  on  nutrition. 

Further,  there  seems  to  be  some  sort  of  functional  relationship 
between  the  thyroid  and  the  pituitary — a  fact  which  lends  some 
corroboration  to  the  view  that  the  pituitary  body  is  in  some  way 
or  another  concerned  in  the  regulation  of  the  nutrition  and  meta- 
bolism of  the  body.  As  has  been  already  pointed  out,  in  some 
cases  of  acromegaly  the  thyroid  gland  is  hypertrophied,  while  in 
others  it  is  atrophied  ;  while  in  some  (?  all)  cases  of  myxcedema 
the  pituitary  body  is  in  some  degree  enlarged. 

In  the  present  state  of  our  knowledge,  it  is  impossible  to  form 
a  definite  conclusion  as  to  the  exact  influence  which  the  enlarge- 
ment of  the  pituitary  body  exerts  in  the  production  of  acromegaly. 
Every  enlargement  of  the  pituitary  body  is  not  attended  with 
symptoms  of  acromegaly.  Two  cases  of  this  kind  have  come 
under  my  own  observation.     Complete  destruction  of  the  pituitary 


ACROMEGALY.  433 

body,  the  result,  for  example,  of  sarcomatous  tumours,  does  not 
necessarily  produce  acromegaly,  though  in  some  cases  of  acromegaly, 
the  enlargement  of  the  pituitary  gland  has  been  sarcomatous  in 
nature.  Again,  it  is  important  to  note  that  the  results  which  have 
up  to  the  present  time  been  obtained  from  the  administration  of 
pituitary  extract  in  cases  of  acromegaly  are  very  contradictory.  In 
a  few  cases  marked  benefit  has  resulted  from  the  treatment,  but  in 
the  majority  of  cases  there  has  either  been  no  improvement,  or  the 
improvement  has  been  so  slight  as  to  be  insufficient  to  warrant  any 
definite  conclusions. 

In  one  of  my  cases,  pituitary  feeding  seemed  to  do  harm,  and 
in  another  to  be  attended  with  benefit.  In  the  former  case  thyroid 
extract  appeared  to  do  good,  and  in  the  latter  harm. 

The  exact  significance  of  the  pathological  alterations  which 
have  been  found  after  death  in  the  sympathetic,  peripheral  nerves 
and  spinal  cord  is  doubtful ;  it  is  possible  that  these  changes  are 
secondary  results  of  either  perverted,  increased,  or  possibly  (though 
this  is  perhaps  less  likely)  diminished  action  of  the  pituitary  gland. 
It  is  quite  conceivable  that  the  pituitary  gland,  like  the  thyroid, 
may  exert  a  marked  influence  upon  the  nutrition  of  the  nervous 
system,  and  that  an  arrested,  increased,  or  perverted  functional 
activity  of  the  pituitary  body  may  lead  to  the  production  of  im- 
portant nutritive  and  structural  changes  in  the  nervous  system  and 
perhaps  in  the  other  tissues  of  the  body.  Further,  the  enlargement 
of  the  thyroid  and  thymus  glands  which  is  frequently  present  in 
cases  of  acromegaly  may  perhaps  be  compensatory  in  character. 
Some  of  the  structural  changes  which  occur  in  acromegaly,  namely, 
the  enlargement  of  the  bones  and  soft  parts,  appear  to  be  of  the 
nature  of  a  hypertrophy  or  overgrowth  ;  others,  such  as  the  changes 
in  the  mammary  glands,  ovaries  and  testes,  are  clearly  atrophic  in 
character. 

Whether  the  pituitary  body  exerts  any  influence  upon  the 
structural  or  functional  condition  of  the  generative  organs,  we  do 
not  at  present  know ;  but  such  a  connection  is  by  no  means 
improbable,  and  the  possibility  of  such  a  relationship  should 
certainly  be  kept  in  view.  The  facts  that  menstruation  is  so 
frequently  arrested  in  the  earlier  stages  of  acromegaly,  and  that 
the  mammary  glands,  ovaries,  and  sometimes  the  testes  atrophy  as 
the  disease  progresses,  are  suggestive  of  this  view.  Further,  the 
fact  that  there  appears  to  be  some  sort  of  relationship  between  the 
thyroid  gland  and  the  ovaries  and  uterus,  and  perhaps  the  mammary 
glands  (for  in  one  of  my  cases  of  myxcedema  the  breasts  became 
full  of  milk  on  the  administration  of  thyroid  extract),  and  between 

2  E 


434  DISEASES   OF   THE   BLOOD   GLANDS. 

the  pituitary  and  thyroid  glands  on  the  other,  perhaps  point  in  the 
same  direction. 

Diagnosis. 

In  typical  and  well  marked  cases  of  acromegaly,  the  diagnosis 
does  not  present  any  great  difficulty.  The  symptoms  are  quite 
peculiar  and  characteristic.  The  physical  alterations  which  are  of 
most  importance  from  a  diagnostic  point  of  view  are:— (i)  The 
marked  enlargement  of  the  extremities  (hands,  feet,  and  face),  an 
enlargement  which  is  not  merely  due  to  an  increase  of  the  bones, 
but  which,  in  part  at  least,  is  the  result  of  an  increase  of  the  soft 
parts  :  (2)  the  shape  of  the  hands  and  fingers,  feet  and  toes,  and  of 
the  nails  ;  the  absence  of  clubbing  of  the  ends  of  the  fingers  and 
toes  is,  according  to  Marie,  a  distinguishing  characteristic  between 
acromegaly  and  hypertrophic  pulmonary  osteo-arthropathy :  (3) 
the  shape  and  conformation  of  the  face  ;  the  marked  elongation  of 
the  lower  part  of  the  face,  the  enlargement  of  the  lower  jaw,  the 
projection  of  the  chin,  the  fulness  and  evertion  of  the  lower  lip,  and 
the  heavy,  somewhat  sad,  expression  of  countenance ;  (4)  the 
increased  growth  of  hair:  (5)  the  development  of  small  peduncu- 
lated warts  on  the  surface  of  the  skin  :  and  (6)  the  atrophy  of 
the  mammary  glands.  While  the  symptoms  which  are  chiefly 
characteristic  are  : — (a)  the  lassitude  and  debility  ;  {b)  the  increased 
tendency  to  sweat ;  (c)  the  arrested  menstruation  ;  (d)  the  myalgic 
and  neuralgic  pains  ;  (e)  the  peculiar  defects  of  vision  (bilateral 
temporal  hemianopsia)  ;  {/)  the  headache  ;  (g)  the  thirst ;  and  {h) 
the  polyuria  or  glycosuria  and  peptonuria  which  are  in  many  cases 
present. 

The  Differential  Diagnosis  of  Acromegaly  and  Myxcedema 
has  already  been  considered  (see  p.  316). 

The  Differential  Diagnosis  of  Acromegaly  and  of  Hyper- 
trophic Pulmonary  Osteo-arthropathy.  —  This  is  much  more 
difficult — indeed,  according  to  some  observers  the  two  conditions 
are  one  and  the  same  disease.  This  view,  however,  seems  a 
mistaken  one. 

The  chief  distinction  between  the  two  diseases  seems  to  be  as 
follows  : — 

In  acromegaly  the  ends  of  the  fingers  are  not  clubbed  ;  whereas 
in  hypertrophic  pulmonary  osteo-arthropathy  marked  clubbing  of 
the  fingers  is  always  present.  In  pulmonary  osteo-arthropathy 
the  enlargement  of  the  fingers  is  especially  noticeable  at  the  last 
phalanx,  the  nails  being  considerably  widened,  lengthened  and, 
more  especially,  curved.      In  pulmonary  osteo-arthropathy  the  toes 


ACROMEGALY.  435 

are  affected  in  a  similar  manner,  though  usually  in  a  less  degree. 
In  acromegaly  the  enlargement  of  the  hands  is  chiefly  in  breadth 
(carpo-metacarpal  region) ;  whereas  in  hypertrophic  pulmonary 
osteoarthropathy  the  enlargement  is  chiefly  of  the  last  or  terminal 
phalanges  of  the  fingers  and  of  the  wrist  joints. 

In  hypertrophic  pulmonary  osteo-arthropathy  the  face,  and 
particularly  the  lower  jaw,  are  not  affected  (enlarged).  In  hyper- 
trophic pulmonary  osteo-arthropathy  the  wrists  and  ankles  are 
notably  enlarged  ;  whereas  in  acromegaly  the  enlargement  of  these 
joints  is  rarely  marked. 

As  the  term  hypertrophic  pulmonary  osteo-arthropathy  denotes, 
the  enlargement  of  the  hands,  feet,  &c,  is  associated  with,  and 
apparently  is  the  result  of,  some  form  of  pulmonary  disease— usually 
chronic  bronchitis,  empyema,  &c.  It  has  been  supposed  by  Marie 
that  the  lung  lesion  leads  to  the  development  of  the  osseous  changes 
by  the  production  and  absorption  into  the  general  circulation  of 
micro-organisms,  or  some  product  of  micro-organisms,  and  that  the 
poison  thus  absorbed  produces  the  structural  changes  which  are 
characteristic  of  the  disease.  In  acromegaly  there  is  no  pulmonary 
lesion. 

Prognosis  and  Treatment. 

The  ultimate  prognosis  in  cases  of  acromegaly  is  unfavourable. 
At  the  present  time  we  do  not  know  of  any  remedial  measures 
which  exert  any  distinctly  beneficial  effect  upon  the  course  of  the 
disease.  The  course  of  the  disease  is  in  most  cases  very  chronic, 
though,  as  has  been  previously  stated,  in  rare  cases  the  disease  runs 
a  more  rapid  course. 

In  some  cases,  nervine  tonics,  more  especially  arsenic  and 
strychnine,  appear  to  be  beneficial.  In  those  cases  in  which  anaemia 
is  prominent,  iron  or  arsenic  should  be  administered.  In  all  cases 
of  the  disease,  pituitary  extract  and  thyroid  extract  deserve  a 
thorough  trial ;  but,  so  far  as  our  present  information  enables  us  to 
judge,  the  effect  of  these  remedies  is  very  uncertain.  In  some  of  the 
recorded  cases  in  which  these  remedies  were  administered,  improve- 
ment, usually  slight  in  degree,  resulted  ;  in  others,  there  was  no 
improvement,  or  the  patients  became  worse.  Thus,  in  eighteen 
cases  tabulated  by  Hinsdale,  in  which  either  pituitary  extract  or 
thyroid  extract  or  both  extracts  were  administered,  there  was  no 
improvement  in  9  cases,  slight  improvement  in  6  cases,  and  great 
improvement  (as  the  result  of  the  administration  of  pituitary 
extract)  in   3   cases. 


436  DISEASES   OF   THE   BLOOD   GLANDS. 


ILLUSTRATIVE    CASES. 


CASE  I .  —  Typical  A cromegaly. 

Female,  aged  27,  single,  admitted  to  the  Edinburgh  Royal  Infirmary  on  25th 
November  1892,  complaining  of  general  weakness  and  enlargement  of  the  hands, 
feet  and  face. 

Previous  history. — The  patient  was  perfectly  well  until  July  1887.  She 
attributes  her  illness  to  a  fall.  Just  before  the  symptoms  of  the  disease  were 
first  noticed,  she  fell  from  a  swing  and  struck  her  right  side ;  the  injury  was  not 
severe.  For  three  weeks  before  this  accident,  she  had  been  subjected  to  a  good 
deal  of  mental  strain  and  overwork  while  nursing  her  grandmother  and  an 
uncle  who  were  ill.  A  short  time  after  the  accident,  her  mother  noticed  that 
she  was  looking  out  of  sorts,  and  that  her  facial  appearance  was  changed. 
About  the  same  time,  the  menstruation,  which  had  always  previously  been 
quite  regular,  became  arrested ;  it  has  never  returned  since.  She  then  began 
to  complain  of  increasing  weakness.  Before  the  disease  commenced,  she  was 
fond  of  exercise  and  could  easily  walk  six  or  eight  miles  without  fatigue ;  during 
the  past  five  years  she  has  never  been  able  to  walk  more  than  four  miles ;  now, 
a  walk  of  half  a  mile  is  as  much  as  she  can  manage  comfortably,  more  than 
that  tires  her. 

Soon  after  the  menstruation  became  arrested,  her  hands,  feet  and  face 
began  to  enlarge.  She  does  not  know  whether  the  enlargement  first  involved 
the  hands,  the  feet,  or  the  face.  The  enlargement  soon  became  considerable. 
Her  face  used  to  be  round;  it  is  now  long  and  oval;  the  alteration  in  her  facial 
appearance  is  so  marked  that  friends  who  have  not  seen  her  since  the  disease 
commenced  now  hardly  recognise  her. 

Family  history. — Unimportant.  Her  father  suffers  from  rheumatism.  She 
has  three  brothers  and  a  sister,  all  healthy.  So  far  as  she  knows,  no  case  of 
acromegaly  has  occurred  amongst  any  of  her  relatives. 

Condition  on  admission. — The  appearance  of  the  patient  is  highly  character- 
istic, the  face,  hands  and  feet  all  being  markedly  enlarged.  The  expression  is 
sad  and  apathetic.  When  the  patient  stands  in  the  erect  position,  the  shoulders 
are  rounded.  The  patient  is  well  nourished;  muscularity  fair;  temperature 
subnormal. 

Complaints. — Debility,  excessive  perspiration  on  exertion,  and  dimness  of 
vision  are  the  chief  complaints.  The  patient  every  now  and  again  suffers  from 
aching  pains  in  the  region  of  the  left  hip.     There  is  no  headache. 

Detailed  description  of  the  appearance  of  different  parts. — The /ace  is  oval 
in  shape,  being  elongated  from  the  nose  to  the  chin.  The  nose  is  very  pro- 
minent and  aquiline;  the  nostrils  and  septum  are  broad,  the  soft  parts  as  well 
as  the  bones  being  evidently  enlarged.  The  lips,  especially  the  lower  lip,  are 
thick.  The  lower  jaw  is  considerably  increased  in  size,  and  the  chin  prominent, 
the  angle  of  the  jaw  being  less  acute  than  normal ;  the  teeth  in  the  lower  jaw 
are  separated  from  one  another  by  considerable  spaces.  The  eyes  are  set  wide 
apart  and  are  very  prominent;  the  left  eyeball  looks  a  little  lower  than  the 
right  and  diverges  slightly  outwards;  the  eyelashes  are  dark  and  abundant;  the 
orbital  fissures  are  comparatively  narrow;  the  eyelids,  especially  those  of  the 


ACROMEGALY.  437 

right  eye,  are  somewhat  swollen ;  the  supra-orbital  ridges  are  very  thick,  and 
the  eyebrows  are  dark  and  bushy.  The  ears  are  not  enlarged.  The  tongue  is 
broad  and  flat ;  its  upper  surface  is  more  ridged  and  grooved  than  normal.  The 
uvula  and  soft  palate  appear  to  be  slightly  swollen.  The  bones  of  the  skull  are 
not  enlarged. 

The  ?teck  is  short  and  thick;  the  head  bent  down  on  the  thorax;  the  larynx 
is  large  and  prominent ;  the  thyroid  gland  can  be  distinctly  felt.  The  clavicles 
and  ribs  are  enlarged,  and  the  antero-posterior  diameter  of  the  chest  increased. 
The  sternum  is  increased  in  size,  the  angle  between  the  manubrium  sterni  and 
the  lower  part  of  the  bone  being  very  marked.  There  is  little  if  any  impair- 
ment of  the  percussion  note  over  the  manubrium  sterni.  The  right  side  of  the 
thorax  measures  considerably  more  than  the  left,  possibly  as  the  result  of  an 
attack  of  inflammation  (?  of  the  pleura)  which  occurred  some  two  or  three 
years  ago. 

The  pelvis  and  pelvic  bones  appear  to  be  enlarged. 

The  hands  are  markedly  enlarged,  increased  in  width  and  thickness  rather 
than  in  length ;  the  soft  parts  project  like  pads  on  the  palmar  aspect ;  the 
fingers  are  flattened.  The  hands  present  a  "battledore"  appearance;  the 
hypothenar  eminences  are  very  prominent.  The  nails  are  wide  but  are  not 
long,  and  do  not  seem  to  be  hypertrophied.  The  wrist  joints  are  slightly 
enlarged  ;  they  are  increased  in  breadth. 

The.  feet  are  markedly  increased  in  size,  especially  in  breadth  ;  the  soles  very 
flat,  the  arch  of  the  foot  being  almost  entirely  obliterated ;  the  first  phalanx  of 
the  great  toe  is  much  elongated,  and  the  metacarpal  bone  is  very  large  and 
lipped  at  its  distal  end.  The  nails  of  the  great  toes  are  square,  and  grooved 
transversely.     The  ankle  joints  are  somewhat  enlarged. 

Integumentary  system. — The  skin  of  the  eyelids  and  of  the  adjacent  parts  of 
the  temples  is  of  a  yellowish  brown  colour,  and  there  are  dirty,  brown-coloured 
patches  on  the  front  of  the  neck  and  over  the  anterior  folds  of  the  axillae ;  the 
patient  states  that  the  discoloration  of  the  neck  and  axillae  has  existed  since 
early  life. 

The  hands  are  usually  cold,  moist  and  clammy  to  the  touch.  The  feet  are 
usually  bathed  in  sweat.  The  hands  frequently  become  cold,  "dead"  and  blanched, 
even  when  the  patient  is  sitting  in  a  warm  room ;  at  other  times,  the  feet  and 
hands,  and  indeed  the  whole  body,  feel  hot  and  flushed.  Numerous  small 
warts  are  scattered  over  the  body,  The  patient  sweats  much  more  profusely 
than  she  used  to  do,  especially  after  exertion. 

The  hair  of  the  head,  eyebrows  and  eyelashes  is  strong  and  wiry,  but  the 
axillary  and  pubic  hairs  are  very  scanty.     There  are  no  hairs  round  the  nipple. 

Nervous  system. —  Well  marked  bilateral  temporal  hemianopsia  is  present ; 
hearing,  smell,  and  taste  are  natural.  There  is  no  headache,  no  vomiting,  and 
no  giddiness.     The  reflexes  are  normal. 

Alimentary  system. — The  appetite  is  good,  but  not  excessive  ;  the  patient 
sometimes  vomits  before  breakfast,  and  frequently  suffers  from  dyspepsia. 

Circulatory  system. — -Heart  normal.  Pulse  somewhat  slow  ;  average  morn- 
ing frequency  60,  evening  72  ;  small,  weak,  of  low  tension,  occasionally  irregular 
in  rhythm.  The  sphygmographic  tracing  shows  a  considerable  degree  of 
dicrotism.     There  is  no  atheroma  of  the  superficial  vessels.     No  cedema. 

Urinary  system.— The  urine  is  normal;  specific  gravity  1,030;  acid;  free 
from  sugar  and  albumen  ;  it  frequently  deposits  a  large  quantity  of  urates. 
The  quantity  of  urine,  instead  of  being  increased,  is  greatly  diminished.    During 


438  DISEASES   OF   THE    BLOOD   GLANDS. 

twenty  days  in  September  (from  the  4th  to  the  23rd  inclusive)  the  average  quantity 
passed  in  the  twenty-four  hours  was  36  ounces,  the  lowest  and  highest  amounts 
tested  on  any  one  day  being  respectively,  14  and  59  ounces. 

Reproductive  system. — Amenorrhoea. 

The  mammary  glands  are  markedly  atrophied,  in  fact  they  cannot  be  felt  ; 
the  nipples,  however,  are  large  and  prominent. 

Blood. — On  admission  to  hospital  the  red  corpuscles  numbered  3,830,000, 
and  the  haemoglobin  equalled  56  %•  After  the  administration  of  iron  and 
arsenic  the  anaemia  soon  disappeared,  and  on  21st  February  1893,  the  red  blood 
corpuscles  numbered  4,540,000  and  the  haemoglobin  equalled  84  %. 

Progress  of  the  case. — The  patient  remained  in  the  hospital  until  25th  April. 
She  was  first  treated  with  iron,  arsenic,  and  thyroid  extract,  and  subsequently 
with  pituitary  extract  (at  first  i  a  pituitary  gland,  subsequently  f  of  a  gland  daily). 
The  pituitary  gland  did  not  produce  any  beneficial  effect ;  under  its  use  the 
sweating  increased.  The  headache  and  other  symptoms  improved  somewhat 
while  she  was  taking  the  thyroid  extract. 

•CASE  II. — Acromegaly  in  a  Giantess. 

Female,  aged  28,  single,  was  admitted  to  the  Edinburgh  Royal  Infirmary  on 
19th  June  1893. 

Previous  history. — Up  to  the  age  of  16,  the  patient  was  no  taller  or  broader 
than  other  girls  of  the  same  age.  After  the  age  of  16,  she  began  to  grow  very 
rapidly,  and  at  20  was  almost  as  tall  as  she  is  now ;  her  shoulders  became 
rounded  and  she  began  to  stoop.  About  the  same  time  (1885),  her  feet  swelled 
and  she  began  to  suffer  from  debility,  headache,  and  excessive  sweating. 
During  the  summer  of  1887,  she  became  short  of  breath  on  exertion,  and  com- 
plained of  pain  in  the  left  side  of  the  abdomen,  swelling  of  the  front  of  the  chest 
and  of  the  breasts  (which  felt  as  if  they  were  full  of  milk),  and  of  pains  in  the 
back  of  the  head.  About  the  same  time,  she  noticed  that  her  hands,  feet,  and 
face  were  notably  enlarged.  Since  the  year  1887,  the  enlargement  of  the  hands, 
feet,  face,  abdomen,  and  in  fact  of  the  whole  body,  has  steadily  increased. 
During  the  whole  of  this  period,  she  has  suffered  more  or  less  from  headache, 
giddiness,  profuse  sweating,  and  gradually  increasing  debility.  For  the  past 
two  years  she  has  been  unable  to  do  anything  except  knit. 

Previous  history  prior  to  the  present  illness. — At  the  age  of  10,  she  had 
scarlet  fever,  and  at  20,  measles ;  she  made  a  good  recovery  from  both  of 
these  diseases.  She  has  had  four  attacks  of  inflammation  of  the  bowels,  each 
lasting  about  a  week;  two  occurred  before  the  age  of  20,  and  two  during  the 
year  1888.  Two  years  ago,  she  suffered  from  left-sided  facial  paralysis  ;  it  came 
on  without  any  apparent  cause. 

Family  history. — The  patient  comes  of  a  healthy  family.  No  case  of  acrome- 
galy or  giantism  has  occurred  amongst  her  relations.  Mer  brothers  and  sisters 
are  all  small  (short)  but  robust  country  people. 

Present  condition. — The  patient  is  a  woman  of  enormous  size.  Height  in 
her  stockings  6  ft.  2  ins.,  and  this  does  not  represent  her  full  height,  for  she  is 
unable  to  stand  erect  owing  to  the  curvature  of  the  upper  part  of  the  spinal 
column.     Her  weight  on  admission  was  24  st.  Z\  lbs. 

The  whole  body  is  increased  in  size,  the  hands,  fret,  and  abdomen  being 
especially  large.  The  feet,  ankles,  and  lower  parts  of  the  legs  are  surrounded 
by  a  solid  oedema,  which  does  not  pit  on  pressure.  The  increased  bulk  of  the 
body  is  obviously  due  to  overgrowth  of  the  bones  as  well  as  of  the  soft  tissues. 


ACROMEGALY.  439 

While  the  patient  stands  in  the  erect  position  the  shoulders  are  seen  to  be 
rounded,  and  the  head  is  bent  forwards  towards  the  sternum. 

Though  well  nourished,  the  patient  is  not  excessively  fat  ;  the  muscles  are 
somewhat  soft ;  the  muscular  power  is  very  defective  (dynamometer  right 
hand  =  43,  left  =  46).     The  gait  is  very  slow,  heavy  and  clumsy. 

The  temperature  is  subnormal,  usually  970  Fahr. 

Complaints. — Extreme  lassitude,  weakness,  and  disinclination  for  exertion 
{for  the  last  two  years,  she  has  not  been  able  to  walk  farther  than  the  length  of 
the  Ward);  headache;  excessive  sweating;  thirst;  vertigo;  and  neuralgic  and 
myalgic  pains  in  different  parts  of  the  body. 

Detailed  description  of  the  appearance  of  different  parts. — Face. — Expression 
sad  and  apathetic.  The  face,  though  massive,  is  not  disproportionately  large 
to  the  other  parts  of  the  body  ;  the  relative  proportion  between  the  upper  and 
lower  parts  of  the  face  is  natural ;  the  facial  conformation  is  not  typical  of 
acromegaly ;  the  lips  are  not  specially  thick,  the  chin  is  not  enlarged,  and  the 
lower  jaw  is  not  prognathous. 

The  left  side  of  the  face  is  flatter  than  the  right  (old  facial  paralysis).  The 
superciliary  ridges  are  not  thickened.  The  eyelids  are  large,  heavy-looking, 
and  drooping.  The  eyebrows,  eyelashes,  eyeballs,  and  ocular  muscles  are 
normal.  The  nose  is  large,  even  for  the  size  of  the  face;  its  bridge  is  pro- 
minent, its  tip  large,  and  the  septum  massive.  The  cheeks  are  full  and  rounded, 
though  not  unduly  prominent.  The  mouth  is,  relatively,  small  ;  the  upper  lip 
of  natural  size;  the  lower  lip  somewhat  full  but  not  everted;  its  colour  is 
natural.  The  ears  are  not  enlarged.  The  palate  is  very  high  and  narrow,  but 
not  V-shaped.  The  lower  jaw  does  not  present  any  characteristic  alterations. 
The  teeth,  many  of  which  are  decayed,  are  not  "  widely  set."  The  gums  are 
inclined  to  be  spongy  and  to  bleed.  The  tongue  is  rather  large  and  flabby. 
The  mouth  is  always  dry,  and  there  is  consequently  some  difficulty  in  swallow- 
ing.    The  buccal  mucous  membrane,  tonsils,  uvula,  and  pharynx  are  normal. 

The  head  is  large  (circumference  64  cm.)  but  normally  shaped;  the  scalp, 
which  is  dry  and  scaly,  is  thickly  covered  with  dark  brown  hair. 

The  neck  is  thick,  but  not  unduly  short.  The  larnyx  is  large,  and  the  pomum 
Adami  prominent.  The  voice  is  soft  in  tone,  and  has  not  changed  since  the 
disease  commenced  ;  the  patient  cannot  sing  so  well  as  she  used  to  do,  being 
unable  to  get  out  high  notes.  The  thyroid  gland  appears  to  be  of  normal  size. 
There  is  no  dulness  over  the  manubrium  sterni. 

Upper  extremity. — The  hands  are  very  large,  but  not  unduly  broad  in  pro- 
portion to  their  length  ;  the  fingers  are  tapered,  the  last  phalanges  being  slightly 
dorsi-flexed.  The  nails  are  well  shaped  and  slightly  grooved  in  the  longi- 
tudinal direction.  The  thenar  and  hypothenar  eminences  are  large  and  soft, 
the  palms  thickly  padded  with  fat.  The  wrists  are  large.  The  bones  of  the 
forearm  and  upper  arm  are  of  great  length,  but  not,  in  proportion  to  their  size, 
unduly  thick. 

The  clavicles  are  well  curved  and  very  long. 

The  chest  is  well  shaped.  Its  circumstance  during  free  inspiration  is  136, 
and  during  expiration  133,  centimetres.  The  condition  of  the  sternum,  ensiform 
cartilage,  and  ribs  does  not  call  for  any  special  remark. 

The  mammce  are  large  and  pendulous  ;  the  nipples  of  normal  size  and  colour  ; 
there  are  no  hairs  round  the  nipples. 

The  abdomen  is  very  large  and  lax  (circumference  at  the  umbilicus  135  cm.). 
The  pelvis  is  very  broad. 


440  DISEASES   OF   THE   BLOOD   GLANDS. 

The  spinal  column  is  curved  forwards  in  the  upper  dorsal  and  cervical 
regions ;  the  spinous  processes  do  not  appear  to  be  enlarged. 

Lower  extremity. — The  feet,  ankles,  and  lower  part  of  the  legs  are  surrounded 
with  a  solid  oedema,  which  does  not  pit  on  pressure;  the  patient  complains  of 
pain  when  firm  pressure  is  made  over  the  swollen  parts.  The  feet  are  very  large, 
square  and  flat ;  like  the  hands,  they  have  increased  greatly  in  size  during  the 
past  six  years;  the  soles  are  very  flat  and  thickly  padded  with  fat;  before  the 
disease  commenced  the  instep  was  high.  The  toes  are  clubbed,  the  first  meta- 
carpal bone  extended  (dorsi-flexed)  and  the  last  phalanx  flexed  (plantar-flexed). 
The  great  toes  are  large.  The  nail  of  the  pollux  is,  relatively  to  the  size  of  the 
toe,  small,  but  well  formed  ;  those  of  the  other  toes  are  small  and  almost  com- 
pletely buried  in  the  soft  parts.  The  bones  of  the  lower  extremities  are  all 
enlarged,  but  not  disproportionately  so. 

The  muscles  are  poorly  developed  ;  the  joints  are  normal. 
Integumentary  system. — The  colour  of  the  skin  is  pale  and  the  texture  much 
coarser  than  it  was  before  the  disease  commenced.  The  skin  is  always  moist ; 
the  patient  perspires  on  the  slightest  exertion  ;  the  sweat  has  a  heavy  odour.  On 
the  face,  abdomen,  back  and  limbs,  there  is  an  excessive  quantity  of  hair.  On 
the  abdomen  two,  and  sometimes  three,  hairs,  which  measure  on  an  average  3 
centimetres  in  length,  spring  from  a  single  hair  follicle.  The  individual  follicles 
are  somewhat  widely  separated  from  one  another.  On  the  upper  lip  and  chin, 
the  growth  of  hair  is  very  considerable.  Numerous  flat  warts,  moles,  freckles 
and  small  stalked  warts,  some  of  them  pigmented,  are  situated  on  the  face, 
limbs,  and  back;  many  of  them  have  developed  since  the  disease  commenced. 

Nervous  system. — Headache,  which  in  the  early  stages  of  the  case  was  con- 
stant and  chiefly  felt  at  the  back  of  the  head,  has  for  the  last  three  or  four  years 
been  intermittent;  it  occurs  daily  and  lasts  for  a  few  hours;  it  is  usually  worse 
during  the  afternoon.  The  pain  is  sharp  and  lancinating  in  character,  and  is 
chiefly  felt  at  the  back  of  the  head  and  over  the  left  temple.  Vertigo  is  a  pro- 
minent symptom,  and  is  chiefly  felt  on  going  to  bed.  Temporary  dimness  of 
vision  and  ringing  in  the  ears  are  also  occasionally  experienced. 

The  superficial  reflexes  are  normal ;  the  knee-jerks  rather  sluggish. 
The  skin  sensibility  to  touch,  pain,  heat  and  cold  is  normal. 
Sight. — The  acuity  of  vision  is  normal.     On  admission,  the  area  for  white 
was  markedly  contracted  in  the  temporal  half  of  the  right  field ;  on  20th  October, 
the  constriction  had  disappeared.     The  conjunctivae  are  healthy.     The  pupils 
and  fundi  oculi  are  normal. 

Smell,  taste  and  hearing  are  normal. 

The  memory  for  recent  events  is  impaired.  The  patient  sleeps  badly  and 
often  wakes  with  a  start. 

Genito-urinary  system. — The  urine  is  scanty  in  amount  (the  average  amount 
for  the  six  days  ending  25th  July,  was  21^  ounces;  and  for  the  seven  days 
ending  24th  September,  27  ounces);  the  specific  gravity  of  the  urine  is  high  (on 
22nd  July,  amount=i2  ounces,  specific  gravity  =  1,043);  the  amount  of  urea 
excreted  in  the  24  hours  is  very  small,  (on  20th  September  =  87.6  grains).  The 
urine  contains  neither  albumen,  sugar,  nor  peptones.  It  frequently  deposits  a 
copious  sediment  of  urates  and  mucus. 

Menstruation  first  appeared  at  the  age  of  23 ;    for  the  first    year   it  was 

irregular;  it  is  now  regular;  the  flow  continues  for  a  week  and  is  always  profuse. 

Circulatory  system. — The  patient  is  breathless  on  the  least  exertion,  and  is 

often  troubled  with  palpitation.    The  heart  is  of  normal  size,  the  impulse  feeble, 


ACROMEGALY.  44-1 

the  sounds  somewhat  indistinct.    The  pulse  averages  67  per  minute  and  is  easily 
compressible.     H ce morrhoids  are  occasionally  troublesome. 

Blood. — The  reds  number  4,880,000  per  c.mm.  ;  haemoglobin  =  80  per  cent. ; 
whites  not  increased ;  reds  normal  in  shape. 

Respiratory  system. — Normal.     The  nose  often  bleeds. 

Digestive  system.— Appetite  small,  patient  has  a  distaste  for  butcher  meat; 
very  thirsty;  digestion  good;  bowels  constipated.  The  stomach,  liver,  and 
spleen  are  of  normal  size. 

Treatment  and  progress  of  the  case.— On  10th  July,  ten  drops  of  thyroid 
extract  (ith  of  a  gland)  once  daily  were  prescribed ;  but  it  was  discontinued  on 
1 6th  July,  the  headache,  sweating  and  feeling  of  lassitude  having  become  markedly 
aggravated. 

On  21st  July,  10  drops  of  pituitary  extract  (-^th  part  of  a  sheep's  pituitary 
gland)  were  given  once  daily.  The  dose  was  gradually  increased  to  15  drops  on 
1st  September;  to  30  drops  on  26th  October;  to  two  fluid  drachms,  three  times 
daily  (fths  of  a  gland)  on  8th  November.  The  remedy  was  steadily  continued 
for  several  months.  During  the  administration  of  this  remedy,  the  symptoms 
(with  the  exception  of  the  giddiness)  were  undoubtedly  relieved;  the  headache 
disappeared;  the  sweating  diminished;  the  feeling  of  debility  and  lassitude 
lessened;  the  constriction  of  the  field  of  vision  disappeared;  and  the  weight 
decreased  from  24  st.  8  lbs.  to  24  st.  But  whether  the  improvement  was  entirely 
due  to  the  pituitary  extract  it  is,  of  course,  impossible  to  say;  I  am  disposed  to 
think  that  the  long  continued  rest  and  careful  treatment  in  hospital  were  in 
part  at  least  responsible  for  the  improvement. 

On  8th  December  1893,  the  patient  was  discharged.  She  was  again  ad- 
mitted to  the  Infirmary  in  September  1895  and  July  1898. 

During  the  seven  years  that  she  has  been  under  my  observation,  the  severity 
of  the  symptoms  (headache,  lassitude,  vertigo,  sweating,  etc.)  has  varied  from 
time  to  time,  but  there  has  been  no  substantial  change  in  her  condition.  There 
has  been  no  increase  in  size  either  in  the  body  as  a  whole,  or  in  its  individual 
parts.  In  short,  she  is  practically  in  the  same  condition  that  she  was  seven 
years  ago. 

CAS  E  III. —  Typical  A  cromegaly. 

R.  L.,  aged  34,  shopman,  married,  seen  at  the  Edinburgh  Royal  Infirmary 
on  6th  May  1896,  suffering  from  typical  acromegaly. 

Previous  history.— The  disease  commenced  gradually  seven  years  ago ;  its 
development  was  preceded  by  an  attack  of  influenza,  which  the  patient  thinks 
was  the  cause.  During  the  past  seven  years  the  patient  has  complained  of 
general  weakness  and  of  headache ;  at  first  the  pain  was  felt  in  the  right  temple ; 
it  is  now  felt  ail  over  the  head.  During  the  past  three  years,  the  fingers  have 
occasionally  become  "  dead." 

Previous  history  prior  to  present  illness. — When  quite  young,  he  suffered 
from  inflammation  of  the  bowels;  this  is  the  only  serious  illness  which  he  has 
ever  had.     He  had  syphilis  twelve  years  ago,  but  has  had  no  "reminders"  since. 

Family  history. — Unimportant.  All  his  near  relatives  are  healthy;  none 
very  tall;  none  of  them  have  suffered  from  rheumatism  or  gout.  His  father, 
aged  69,  and  his  mother,  aged  69,  are  both  alive  and  healthy.  He  has  four 
brothers  and  one  sister,  aged  32  to  45,  all  alive  and  in  good  health.  He  has 
two  children  of  his  own,  both  girls;  both  are  healthy.  His  wife  has  had  no 
miscarriages. 


4-p  DISEASES   OF   THE   BLOOD   GLANDS. 

Complaints. — Ke  complains  of  great  weakness,  headache,  occasional  giddi- 
ness, deafness,  and  noises  in  the  ears.  He  is  able  to  walk  very  little;  before 
the  illness  commenced  he  could  walk  ten  miles  without  difficulty;  now  he  feels 
tired  if  he  goes  ten  yards;  is  inclined  to  sit  whenever  he  gets  a  chance. 

Present  condition.— Height  5  ft.  7  ins.;  weight  12  st.  7  lbs.  He  states  that 
he  has  grown  one  and  a  half  inches  since  the  disease  commenced,  and  that 
when  he  married  seven  years  ago  (this  was  just  before  the  disease  commenced) 
he  only  weighed  9  st. ;  he  is  much  stouter  and  broader  than  he  used  to  be.  His 
hands,  which  are  very  broad  and  short,  are  much  larger  than  they  used  to  be; 
he  used  to  take  size  "j\  in  gloves,  he  now  takes  9^.  His  head  has  also  increased 
in  size  ;  he  used  to  take  a  hat  No.  6f  in  size,  he  now  takes  a  hat  No.  7  in  size.  His 
feet  have  also  increased  greatly  in  size ;  he  used  to  take  No.  6  in  boots,  he  now 
takes  No.  9.     The  feet  are  short.     The  toes  are  very  big  and  broad  at  the  tips. 

His  face  has  changed  very  much  in  appearance.  The  lower  jaw  has,  he 
says,  shot  out ;  the  forehead  projects  more  than  it  used  to  do,  the  supra-orbital 
ridges  being  enlarged.  The  lower  lip  is  enlarged.  The  nose  is  much  broader 
than  it  used  to  be.  Ears  not  much  altered.  The  tongue  is  very  much  enlarged. 
The  teeth  of  the  lower  jaw  are  separated  from  one  another  by  large  spaces. 
Gums  natural.     Cannot  breathe  through  his  nose. 

The  neck  is  short  and  thick;  the  thyroid  gland  is  not  enlarged;  there  is  no 
area  of  dulness  over  the  manubrium  sterni.  His  tone  of  voice  has  become 
changed;  it  is  much  harsher  and  rougher  than  it  used  to  be;  he  used  to  have  a 
clear  tenor  voice. 

There  is  a  marked  antero-posterior  curvature  of  the  spine  in  the  cervical  and 
upper  dorsal  regions;  also  slight  lateral  curvature  towards  the  left. 

Skin. — Every  now  and  again,  he  has  a  feeling  of  heat  and  flushing,  at  other 
times  of  cold.  The  hair  and  eyebrows  are  not  changed.  He  sweats  a  good 
deal,  especially  about  the  head.  Numerous  small  warts  have  developed  on  the 
skin;  there  are  also  numerous  freckles  on  the  extensor  aspects  of  the  arms,  on 
the  buttocks  and  thighs.     Slight  petechia;  occasionally  develop  on  the  skin. 

No  increase  of  saliva.     For  some  time  has  had  a  "terrible  watering"  from 
the  eyes  and  nose. 

Appetite  is  poor,  much  smaller  than  it  used  to  be;  he  is  very  thirsty,  especi- 
ally at  night.  The  bowels  have  become  very  constipated  since  the  illness 
commenced. 

Urine  clear  amber  coloured;  specific  gravity  1,032;  no  sugar;  slight  trace 
of  albumen. 

Genital  organs  are  not  enlarged.  Sexual  power  decidedly  less  than  it  used 
to  be. 

Nervous  system. — Headache  is  more  or  less  continuous,  and  is  felt  over  the 
whole  head.  There  has  been  no  vomiting  and  very  little  giddiness.  Complains 
of  rushing  noises  in  the  ears  and  deafness.  Sleeps  fairly  well,  if  it  were  not  for 
the  pains  in  the  head. 

Six  months  ago  his  sight  was  normal;  he  now  complains  of  slight  dimness  in 
the  left  eye.  Acuity  of  vision  in  the  right  eye=|5,  left  eye  =  ilr;  the  fields  of 
vision  are  normal.  Pupils  equal  and  active  both  to  light  and  accommodation. 
He  lias  been  deaf  in  both  ears  for  nearly  two  years. 

Treatment. — The  patient  stated  that  during  the  course  of  his  illness  he  had 
been  treated  both  with  thyroid  extract  and  pituitary  extract  ;  these  remedies 
brought  down  his  weight,  but  did  not  relieve  the  headache.  Was  advised  to 
continue  the  pituitary  extract,  which  he  has  been  taking  in  larger  doses.  He 
was  only  seen  once.     The  subsequent  progress  of  the  case  is  not  known. 


APPENDIX. 


The  condition  of  the  nails  in  chlorosis. — In  many  cases  of 
chlorosis  the  nutrition  of  the  nails  is  markedly  affected  ;  they  are 
apt  to  become  thin  and  flat,  in  some  cases  ridged  longitudinally,  in 
others  concave  instead  of  convex. 

Pernicious  anaemia.  —  Case  XXVI.  (page  120):  this  patient 
died  in  January  1899.  Case  XLIII.  (page  133):  this  patient  died 
in  November  1898. 

Addison's  disease. — Since  the  article  was  written  I  have  had 
another  case  in  which  the  most  marked  improvement  resulted  from 
the  administration  of  suprarenal  extract.  The  case  was  shown  at 
a  recent  meeting  of  the  Edinburgh  and  neighbouring  Branches  of 
the  British  Medical  Association,  and  will  shortly  be  published  in 
the  British  Medical  Journal. 

Leucocythsemia. — The  case  reported  on  page  171  relapsed  and 
died  soon  after  the  sheet  containing  the  report  was  printed.  The 
result  of  the  post-mortem  examination  will  shortly  be  published 
in  full. 


INDEX. 


Acromegaly,  421 

cases  of,  436 

clinical  history  of,  422 

course  of,  422 

diagnosis  of,  434 

etiology  of,  421 

historical  note  on,  421 

morbid  anatomy  of,  431 

pathological  physiology  of,  431 

prognosis  in,  435 

symptoms  of,  429 

treatment  of,  435 

varieties  of,  430 
Addison,  Dr,  56,  57,  212,  215 
Addison's  disease,  212 

cases  of,  234,  267 

clinical  history  of,  215 

clinical  types  of,  235 

complications,  234 

definition  of,  212 

diagnosis  of,  238 

duration  of,  236 

etiology  of,  214 

historical  note  on,  212 

mode  of  death  in,  237 

morbid  anatomy  of,  246 

nature  of  capsular  lesion  in,  256 

pathological  classification  of,  236 

pathological  physiology  of,  257 

prognosis  in,  262 

synonyms,  212 

treatment  of,  263 
Alezais,  Dr,  226,  241,  249,  253,  254,  256 
Alimentary  system,  condition  of — 

in  acromegaly,  429 
„  Addison's  disease,  221 
„  chlorosis,  41 

„  exophthalmic  goitre,  398,  402 
,,  Hodgkin's  disease,  194 
„  leucocythaemia,  160 
„  myxcedema,  310 
„  pernicious  anaemia,  72> 
„  sporadic  cretinism,  321 
Allbutt,  Professor  Clifford,  25 
Allison,  Dr,  76 
Amenorrhcea — see  Uterine  functions 


Anaemia,  3 

causes  of,  5,  7 

classification  of,  3,  21 

clinical  symptoms  associated  with, 
10 

cytogenetic,  3 

definition  of,  3 

essential — see  Pernicious  anaemia 

etiology  of,  3 

idiopathic — see  Pernicious  anasmia 

in  Addison's  disease,  228 

primary,  3 

scientific  classification  of,  5 

secondary,  4 

symptomatic,  4 
Ankylostoma  duodenale,  6,  yy 
Anstie,  Dr,  43 
Appendix,  443 
Arsenic,  as  a  cause  of  anaemia,  6 

in  Hodgkin's  disease,  209 

„  leucocythaemia,  169 

„  pernicious  anaemia,  95,  100,  105 


Balfour,  Dr  G.  W.,  39 

Barrs,  Dr,  106 

Bennett,  Professor  J.  Hughes,  139 

Bienfait,  Dr,  410 

Biermer,  Professor,  56,  76 

Blood,  clinical  examination  of,  15 
condition  of — 
in  Addison's  disease,  228 
„  anaemia,  15 
„  chlorosis,  32 
„  exophthalmic  goitre,  402 
„  Hodgkin's  disease,  192 
„  leucocythaemia,  147,  153 
„  myxcedema,  309 
„  pernicious  anaemia,  60 

Blood-destruction,  seats  of,  8 

Blood-formation,  seats  of,  8 

Blood-plates,  20 

Bone-marrow,  condition  of — 
in  Hodgkin's  disease,  181 
„  leucocythaemia,  150 
■  „  pernicious  anaemia,  79 


446 


INDEX. 


Bone-marrow,  condition  of — continued. 
in  the     treatment    of     pernicious 
anaemia,  106 

Bonfils,  Dr,  179 

Brain,  condition  of — 
in  acromegaly,  428 
„  exophthalmic  goitre,  409 
,,  leucocythaemia,  161 
„  myxcedema,  305 
,,  pernicious  anaemia,  77,  81 
„  sporadic  cretinism,  321 

Bramwell,  Dr  Edwin,  30 

Bright's  disease,  as  a  cause  of  anaemia,  6 

Brunton,  Dr  T.  L.,  52,  107 

Buhl,  Dr,  229 

Bunge,  Dr,  26 


Cabot,  Dr,  33,  36,  38,  64,  67,  96,  155, 

158,  165,  194,  207 
Cancer  of  suprarenal  capsules,  249 
Carbonic  acid  gas,  inhalations  of,  in 

leucocythaemia,  171 
Carrington,  Dr,  245 
Charcot,  Professor,  298,  385,  401 
Chauffard,  Dr,  246 
Chauveau,  Dr,  40 
Cheeks,  pink  blush  on,  in  myxcedema, 

300 
Chlorosis,  22 

blood  in,  32 

cases  of,  34,  37 

clinical  history  of,  31 

definition  of,  22 

diagnosis  of,  44 

etiology  of,  22 

general  appearance  in,  31 

prognosis  in,  48 

symptoms  in,  32 

synonyms,  22 

theories  as  to  causes  of,  24 
Clark,  Sir  Andrew,  12,  26 
Colour-index,  16,  35 
Constipation,  in  anaemia,  12 
Convergence  of  eyeballs,  in  exophthal- 
mic goitre,  395 
Copeman,  Dr,  67,  106 
Coupland,  Dr  Sydney,  248,  261 
Crocker,  Dr,  245 
Croom,  Dr  Halliday,  292 
Cytogenetic  anaemia,  3 


Danford,  Dr,  106 
Davy,  Dr,  66 
Debility,  in  anaemia,  11 
Delepine,  Professor,  246 
Diarrhoea,  as  a  cause  of  anaemia,  6 

in  anaemia,  12 

„  exophthalmic  goitre,  398 


Digestive  system — see  Alimentary  sys- 
tem 
Dreschfeld,  Professor,  184,  185,  399 
Drummond,  Dr  D.,  399 
Dyspeptic  symptoms,  in  anaemia,  12 


Ebstein,  Professor,  162 
Ehrlich,  Professor,  19 
Eichhorst's  corpuscles,  18 
Eichhorst,  Professor,  18 
Electrical  resistance  of  the  skin — 

in  exophthalmic  goitre,  398 
„  myxcedema,  303 
Emaciation — 

in  Addison's  disease,  231 
,,  Hodgkin's  disease,  191 
Eosinophile  cells,  20 
Essential     anaemia  —  see     Pernicious 

anaemia 
Ewart,  Dr  W.,  171 
Excision  of  the  spleen,  170 
Exophthalmic  goitre,  381 

cases  of,  404 

clinical  history  of,  385 

contrasted  with  myxcedema,  41 1 

course  of,  403 

definition  of,  381 

diagnosis  of,  415 

etiology  of,  382 

historical  note  on,  381 

morbid  anatomy  of,  408 

pathological  physiology  of,  409 

prognosis  in,  416 

symptoms  of,  386 

treatment  of,  418 
Eyes,  running  at,  in  myxcedema,  304 

prominence   of,   in    exophthalmic 
goitre,  393 


Fainting',  in  anaemia,  10 
Fenwick,  Dr  Samuel,  78 
Fever — see  Temperature 

in  anaemia,  13 
Filene,  Professor,  410 
Finny,  Dr,  226,  237,  262 
Flushing  in  exophthalmic  goitre,  397 
Foetid  odour  of  the  body,  in  Addison's 

disease,  233 
Fowler,  Dr  J.  S.,  163 
Fowler,  Dr  K.,  40 
Fox,  Dr,  324 
Franks,  Dr  Kendal,  238 
Fraser,  Professor  T.  R.,  106 
Friedreich,  Professor,  409 
Fundus  oculi,  condition  of — 

in  acromegaly,  427 

„  chlorosis,  43 

„  leucocythaemia,  159 


INDEX. 


447 


Fundus  oculi,  condition  of— continued. 
in  pernicious  anaemia,  70 


Gage,  Dr,  251 

Genital  organs,  non-development  of — 
in  Addison's  disease,  233 
„  sporadic  cretinism,  321 
Gibson,  Dr  G.,  107 
Giddiness,  in  anaemia,  10 
Gowers,  Sir  Wm.,  178,   187,   192,  195, 

201,  253 
Graefe's  symptom,  395 
Graves'    disease  —  see    Exophthalmic 

goitre 
Greenfield,  Professor,  408,  410 
Greenhow,  Dr,  214,  222,  224,  225,  227, 

230,  232,  251,  265 
Gull,  Sir  Wm.,  237,  262,  287 
Gulland,  Dr,  8,  65,  76,  87 


Handford,  Dr,  192,  209 

Hanot,  Dr,  246 

Haemoglobin,  estimation  of,  16 

relative  richness  in  individual  red 
corpuscles,  16 
Haemorrhage,  as  a  cause  of  anaemia,  5 

in  anaemia,  12 

occurrence  of — 

in  chlorosis,  43 
„  Hodgkin's  disease,  194 
„  leucocythaemia,  148,  159 
„  myxcedema,  310 
,,  pernicious  anaemia,  70,  78 
Hair,  condition  of — 

in  acromegaly,  427 

„  exophthalmic  goitre,  399 

,,  myxcedema,  303 

,,  sporadic  cretinism,  320 
Headache,  in  anaemia,  12 
Heart,  condition  of — 

in  acromegaly,  428 

„  Addison's  disease,  217,  255 

,,  anaemia,  13 

„  chlorosis,  38 

,,  exophthalmic  goitre,  388 

,,  Hodgkin's  disease,  194 

,,  leucocythaemia,  150,  159 

,,  myxcedema,  309  . 

„  pernicious  anaemia,  69,  78 
Henry,  Dr  F.  P.,  213 
Hodgkin,  Dr,  177 
Hodgkin's  disease,  176 

blood  in,  192 

clinical  history  of,  185 

clinical  types  of,  199 

course  of,  199 

definition  of,  176 


Hodgkin's  disease — continued. 

diagnosis  of,  201 

duration  of,  199 

etiology  of,  182 

historical  note  on,  177 

mode  of  death  in,  201 

morbid  anatomy  of,  179 

onset  and  course  of,  185 

prognosis  in,  208 

synonyms,  176 

treatment  of,  209 
Hoffmann,  Professor,  289 
Horsley,  Professor   Victor,    290,    295,. 

297 
Hunn,  Dr  H.,  290,  291,  302,  311 
Hunter,  Dr  Wm.,  6,  56,  72,  79,  82,  91,. 

106,  107 
Hutchison,  Dr  Robert,  327 


Idiopathic    anasmia  —  see     Pernicious 
anaemia 

Immermann,  Professor,  76 

Index,  colour — see  Colour-index 

Integumentary  system,  condition  of — 
in  acromegaly,  426 
,,  Addison's  disease,  222 
,,  chlorosis,  31 
„  exophthalmic  goitre,  397 
,,  Hodgkin's  disease,  192 
,,  leucocythaemia,  158 
,,  myxcedema,  302 
„  pernicious  anaemia,  59 
,,  sporadic  cretinism,  320 

Intestinal    antiseptics,    in    pernicious, 
anaemia,  106 

Intestine,  condition  of — 

in  Addison's  disease,  255 

„  myxcedema, 

„  pernicious  anaemia,  78 

Ireland,  Dr,  288 

Iron,  in  chlorosis,  50,  52 

,,  pernicious  anaemia,  107 


Jaccoud,  Professor,  214 
Jones,  Dr  Lloyd,  29,  yj 


Kidneys,  condition  of — 
in  acromegaly,  428 
„  Addison's  disease,  232 
„  exophthalmic  goitre,  400 
,,  Hodgkin's  disease,  198 
„  leucocythaemia,  151 
,,  myxcedema,  310 
„  pernicious  anaemia,  79 
„  sporadic  cretinism,  322 

Kussmaul,  Professor,  221 


443 


INDEX. 


Laschkewitsch,  Dr,  229 
Lead,  as  a  cause  of  anaemia,  6 
Leucocythaemia,  139 
acute,  162,  164 
blood  condition  in,  153 
clinical  history  of,  151 
definition  of,  139 
diagnosis  of,  163 
etiology  of,  144 
historical  note  on,  139 
morbid  anatomy  of,  147 
prognosis  in,  168 
synonyms,  139 
treatment  of,  169 
varieties  of,  141 
Leukaemia — see  Leucocythaemia 
Lichtheim,  Professor,  74 
Liver,  condition  of — 

in  Hodgkin's  disease,  181,  196 
,,  leucocythaemia,  150,  153 
„  pernicious  anaemia,  79 
Lymphatic     anaemia — see    Hodgkin's 
disease 
glands,  condition  of — 
in  acromegaly,  429 
„  Addison's  disease,  255 
„  Hodgkin's  disease,  179, 187, 

196 
„  leucocythaemia,  149 
„  sporadic  cretinism,  321 
Lymphocytes,  19 

Lymphoid     deposits,     in     Hodgkin's 
disease,  181 


M'Dowall,  Dr  T.  W.,  214 

Mackenzie,  Dr,  290 

Mackenzie,  Dr  Hector,  324 

Mackenzie,  Dr  Stephen,  21,  62,  96 

Mackern,  Dr,  66 

M'Munn,  Dr,  262 

Malaria,  as  a  cause  of  anaemia,  6 

condition  of  the  white  corpuscles 
in,  165 

Mann,  Dr  Dixon,  233,  260 

Marie,  Professor,  409 

Marinesco,  Professor,  409 

Marks,  Dr,  252 

Marrow     of    the     bones — see    Bone- 
marrow 

Max  Schultze's  granular  masses,  21 

Megalocytes,  17 

Mendel,  Dr,  409 

Menorrhagia — see  Uterine  functions 

Menstruation — see  Uterine  functions 

Mercury,  as  a  cause  of  anaemia,  6 

Merkel,  Dr,  224,  230,  256 

Microcytes,  17 

M  icro-organisms — 

in  Hodgkin's  disease,  183,  184 


Micro-organisms — continued. 

in  leucocythaemia,  145,  163 

„  pernicious  anaemia,  66,  82 
Minnich,  Professor,  74 
Mobius,  Professor,  395,  410 
Morner,  Dr,  26 
Mossop,  Dr,  273 
Mott,  Dr,  72 

Muir,  Professor  R.,  6,   18,  20,  36,  65, 
80,  141,  143,   145,  154,  156,  157, 
193,  275,  4o8 
Murray,  Dr  G.,  289,  290,  324,  410 
Musser,  Dr,  75 
Myelocytes,  30 
Myxcedema  287 

cases  of,  312,  325,338 

clinical  history  of,  298 

contrasted     with       exophthalmic 
goitre,  41 1 

course  of,  311 

definition  of,  287 

diagnosis  of,  314 

etiology  of,  289 

historical  note  on,  287 

pathological  physiology  of,  296 

prognosis  in,  317 

symptoms  of,  312 

treatment  of,  323 


Nails,  condition  of — 
in  acromegaly,  423 
„  Addison's  disease,  226 
„  chlorosis — see  the  Appendix 
„  exophthalmic  goitre,  400 
,,  myxcedema,  304 

Nervous  symptoms  in  anaemia,  10 

Nervous  system,  condition  of — 
in  acromegaly,  423 
„  Addison's  disease,  230 
„  chlorosis,  43 

,,  exophthalmic  goitre,  396,  401 
,,  Hodgkin's  disease,  198 
„  leucocythaemia,  160 
,,  myxcedema,  305 
„  pernicious  anaemia,  74 
„  sporadic  cretinism,  321 

Nervousness,  in  exophthalmic  goitre, 
396 

Neumann,  Professor,  150 

Niemeyer,  Professor,  25 

Nonne,  Professor,  74 

Nose,  running  at,  in  myxcedema,  304 

Nucleated  red  corpuscles,  18 


(Edema  of  the  feet,  in  anaemia,  10 
Oligaemia,  1 
Oligochromaemia,  I 
Oligocythaemia,  1 


INDEX. 


449 


Oliver,  Dr,  220  » 

Ollivier,  Professor,  160 
Optic  neuritis — see  Fundus  oculi 
Ord,  Dr,  287,  300,  305 
Osier,  Professor,  192,  197,  203 
Oxygen  inhalations,  in  leucocythaemia, 
170 
in  pernicious  anaemia,  108 


Paget,  Professor,  254 
Pallor,  in  anaemia,  10 
Palpitation,  in  anaemia,  11 
Pepper,  Professor  W.,  85 
Pernicious  anaemia,  56 

blood  condition  in,  60 

cases  of,  109 

cases  treated  with  arsenic,  100 

clinical  history  of,  56 

definition  of,  56 

diagnosis  of,  89 

etiology  of,  75,  83 

historical  note  on,  56 

mode  of  onset  of,  yy 

morbid  anatomy  of,  yy 

pathological  physiology  of,  82 

prognosis  in,  94 

synonyms,  56 

treatment  of,  99 
Peripheral    irritation,    as    a    cause  of 

Hodgkin's  disease,  183 
Petechial  haemorrhages,  in  pernicious 

anaemia,  78 
Pigmentation    of    the    mucous    mem- 
branes,   in    Addison's    disease, 
222 
Pigmentation  of  the  skin,  causes  of,  243 

in  Addison's  disease,  222 

„  exophthalmic  goitre,  399 

„  myxcedema,  300 

„  pernicious  anaemia,  145 
Pituitary  gland,  condition  of — 

in  acromegaly,  429 

„  myxcedema,  294 
Plates,  blood — see  Blood-plates 
Poikilocytosis,  18 
Potain,  Professor,  40 
Primary  anaemia — see  Anaemia 
Pruden,  Dr  M.,  290,  291,  302,  311 
Pseudo  -  leukaemia  —  see       Hodgkin's 

disease 
Pulmonary  systolic  murmur,  in  anaemia, 

39 
Pulse,  condition  of — 
in  acromegaly,  428 
„  Addison's  disease,  220 
„  chlorosis,  38 
„  exophthalmic  goitre,  389 
„  Hodgkin's  disease,  194 
„  leucocythaemia,  159 


Pulse,  condition  of — continued. 
in  myxcedema,  309 
„  pernicious  anaemia,  69 

Pupil,    condition    of,   in   exophthalmic 
goitre,  394 

Pye-Smith,  Dr,  3,  57,  75,  223 


Quincke,  Professor,  62,  96 
Quinine,  in  leucocythaemia,  164,  169 


Ransom,  Dr  W.  B.,  79,  87 

Ranvier,  Professor,  160 

Red  corpuscles,  estimation  of,  15 

nucleated,  18 

seat  of  destruction  and  formation 
of,  8 

size  and  shape  of,  17 
Respiratory  system,  condition  of — 

in  exophthalmic  goitre,  400 

„  Hodgkin's  disease,  198 

„  leucocythaemia,  162 

,,  pernicious  anaemia,  72 
Rethers,  Dr,  26 
Retinal    haemorrhages  —  see   Fundus 

oculi 
Rickets,  as  a  cause  of  anaemia,  7 
Robertson,  Dr  Aitchison,  292 
Rolleston,  Dr,  252,  259 
Russell,  Dr  Risien,  74,  81 
Russell,  Dr  W.,  40 


Saliva,  increased  flow  of,  in  myxcedema, 

Sanderson,  Professor  Burdon,  230 

Sansom,  Dr,  40,  41 

Schafer,  Professor,  220 

Secondary  anaemia — see  Anaemia 

Semmola,  Professor,  261 

Sexual  organs,  in  sporadic  cretinism, 
321 

Shadow-corpuscles,  66 

Shortness  of  breath,  in  anaemia,  10 

Skin — see  Integumentary  system 

Spinal  cord,  condition  of — 
in  acromegaly,  431 
„  Addison's  disease,  256 
,,  Hodgkin's  disease,  197 
„  leucocythaemia,  148 
,,  pernicious  anaemia,  74,  81 

Spleen,  condition  of — 

in  Addison's  disease,  255 
„  Hodgkin's  disease,  181,  195 
„  leucocythaemia,  148,  153 
„  pernicious  anaemia,  79 

Spleen,  excision  of,  170 

Splenic  anaemia,  94,  168 


2  F 


45o 


INDEX. 


Sporadic  cretinism,  318 

clinical  history  of,  318 

diagnosis  of,  322 

etiology  of,  318 

prognosis  in,  322 

treatment  of,  323,  329 
Sprue,  as  a  cause  of  anaemia,  6 
Stelhvag's  symptom,  395 
Stengel,  Dr,  165,  172 
Stockman,   Professor,   9,    25,    26,    27, 

107 
Stomach,  condition  of— 

in  acromegaly,  429 

„  Addison's  disease,  255 

„  pernicious  anaemia,  78 
Supraclavicular    swellings,  in   myxce- 

dema,  301 
Suprarenal  capsules,  cancer  of,  249 

fatty  transformation  of,  248,  272 

simple  atrophy  of,  247 

tubercular  disease  of,  246 

unilateral  disease  of,  254 
Suprarenal      extract,     in      Addison's 

disease,  265,  274 
Sweating,  diminished,  in  myxcedema, 

302 
Sweating,  excessive — ■ 

in  acromegaly,  426 

„  exophthalmic  goitre,  397 
Sympathetic  nerves,  condition  of — 

in  acromegaly,  431 

„  Addison's  disease,  248,  253,  258, 
261 

„  exophthalmic  goitre,  409 

„  pernicious  anaemia,  58 
Symptomatic  anaemia,  4 


Taylor,  Dr  James,  74,  81 

Temperature,  the  condition  of — 
in  Addison's  disease,  231 
„  chlorosis,  43 
„  exophthalmic  goitre,  398 
„  Hodgkin's  disease,  194 
,,  leucocythaemia,  162 
,,  myxcedema,  308 
,,  pernicious  anaemia,  71 
„  sporadic  cretinism,  320 

Thomson,  Mr  Alexis,  196 

Thomson,  Dr  John,  323 

Thrombosis,  venous — 
in  chlorosis,  41 
,,  in  Hodgkin's  disease,  198 
„  leucocythaemia,  159 

Thymus  gland,  condition  of — 
in  acromegaly,  429 
„  exophthalmic  goitre,  408 
„  Hodgkin's  disease,  181 
„  leucocythaemia,  150 
„  myxcedema,  294 


Thyroid  extract — 

in  acromegaly,  435 
„  exophthalmic  goitre,  419 
„  Hodgkin's  disease,  211 
„  myxcedema,  325,  328 
„  sporadic  cretinism,  326,  329 
Thyroid  gland,  condition  of — 
in  acromegaly,  429 
„  chlorosis,  32 

„  exophthalmic  goitre,  391,  408 
,,  Hodgkin's  disease,  181 
,,  myxcedema,  293,  301 
,,  sporadic  cretinism,  318 
Transfusion,    in    pernicious    anaemia, 

108,  193 
Tremor,  in  exophthalmic  goitre,  396 
Trousseau,  Professor,  25,  178,  183,200 
Tubercle  of  lymphatic  glands,  resem- 
bling Hodgkin's  disease,  188,203 

Urine — 

in  acromegaly,  428 
„  Addison's  disease,  232 
,,  anaemia,  14 
„  chlorosis,  43 
„  exophthalmic  goitre,  400 
,,  Hodgkin's  disease,  198 
,,  leucocythaemia,  160 
,,  myxcedema,  310 
,.  pernicious  anaemia,  71,  91 
,,  sporadic  cretinism,  322 
Uterine-ovarian  functions — 

in  acromegaly,  429 
„  Addison's  disease,  233 
„  chlorosis,  42 
,,  exophthalmic  goitre,  403 
,,  leucocythaemia,  145 
,,  myxcedema,  310 
,,  sporadic  cretinism,  321 

Virchow,  Professor,  25,  140,  154 

Vomiting — 

in  acromegaly,  427 

„  Addison's  disease,  221 

„  chlorosis,  42 

,,  exophthalmic  goitre,  399 

,,  pernicious  anaemia,  73 

Weight,  loss  of,  in  Addison's  disease, 

231 
White  corpuscles,  18 

seats  of  formation  of,  8 

varieties  of,  19 
White,  Dr  Hale,  73,  81,  95 
Whyte,  Dr  Mackie,  292 
Wilks,  Sir  Samuel,  56,  178,   194,  225 

228,  237,  238,  250 
Wolfenden,  Dr,  398 

Yeo,  Dr  Burney,  392 


CATALOGUE 
No.   1. 


READ  "SPECIAL  NOTE"   BELOW. 

APRIL,  1899. 

CATALOGUE 

OF 

edical,  Dental, 

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PATHOLOGY. 
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Blackburn.     Autopsies.  1.25 

Blodgett.  Dental  Pathology  1.25 
Coplin.  Manual  of.  265  Illus.  300 
Gilliam.     Essentials  of.     -  .75 

Hall.  Compend.  Illus.  2d  Ed.  .80 
Hewlett.  Bacteriology.  -  3.00 
Virchow.     Post-mortems.  .75 

Whitacre.  Lab.  Text-book.  1.50 
Williams.     Bacteriology.         1.50 

PHARMACY 
Beasley's  Receipt-Book.      -    2.00 

Formulary.      -        -  2.00 

Coblentz.  Manual  of  Pharm.  3.50 
Proctor.  Practical  Pharm.  3.00 
Robinson.  Latin  Grammar  of.  1.75 
Sayre.    Organic  Materia  Med. 

and  Pharmacognosy.      -  — 

Scoville.     Compounding.  2.50 

Stewart's  Compend.  5th  Ed.  .80 
U.   S.   Pharmacopoeia.     7th 

Revision.  CI.  2.50  ;  Sh.,  3.00 

Select  Tables  from  U.  S.  P.       .25 

PHYSIOLOGY. 
Brown.     Physiol,  for  Nurses.    .75 
Brubaker's  Compend.     Illus- 
trated.    9th  Ed.       -        -          .80 
Kirke's  New  15th  Ed.    (Halli- 
burton.)   Cloth,  3.00;    Sh.,  3.75 
Landois'  Text-book.  845  Illus- 
trations. -  -        

Starling.  Elements  of.  •  1.00 
Stirling.  Practical  Phys.  2.00 
Tyson's  Cell  Doctrine.  -  1.50 
Yeo's  Manual.     254  111.  2.50 

POISONS. 
Murrell.     Poisoning.         -        1.00 
Reese.    Toxicology.    4th  Ed.   3.00 
Tanner.     Memoranda  of.  .75 

PRACTICE. 
Beale.     Slight  Ailments.  1.25 

Fowler's  Dictionary  of.  -  3.00 
Hughes.  Compend.  2  Pts.  ea.    .80 

Physicians'  Edition. 

1  Vol.  Morocco,  Gilt  edge.  2.25 
Roberts.  Text-book.  9th  Ed.  4.50 
Taylor's  Manual  of.     -  4.00 

Tyson.    The  Practice  of  Medi- 
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Davis.     Materia  Medica  and 

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Impey.  Leprosy.  -  -  3.50 
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Van   Harlingen.     Diagnosis 

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DISEASES. 
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Deaver.     Appendicitis.        -     3.50 

Surgical  Anatomy.      .  21.00 

Dulles.  Emergencies.  -  1.00 
Hamilton.  Tumors.  3d  Ed.  1.25 
Heath's  Minor.  10th  Ed.  1.25 
Diseases  of  Jaws.       -     4.50 

Lectures  on  Jaws.  .50 

Horwitz.  Compend.  5th  Ed.  .80 
Jacobson.  Operations  of.  -  3.00 
Lane.     Surgery  of  Head.  5.00 

Macready  on  Ruptures        -    6.00 
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Morris.     Renal  Surgery.  2.00 

Moullin.      Complete     Text- 
book.    3d  Ed.  by  Hamilton, 
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Plates.  CI.  6.00;  Sh.    7.00 


Roberts'  Fractures.          -  #1.00 

Smith.     Abdominal  Surg.  10. co 

Swain.     Surgical  Emer.       -  1.75 

Voswinkel.  Surg.  Nursing.  1.00 

Walsham.     Practical  Surg.  3  00 

Watson's  Amputations.  5.50 

TECHNOLOGICAL  BOOKS. 
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Gardner.     Brewing,  etc.  1.50 

Gardner.    Bleaching   and 

Dyeing.    ...         -         1.50 
Groves  and  Thorp.    Chemi- 
cal   Technology.       Vol.     I. 
Mills  on  Fuels.         -         CI.  5.00 
Vol.  II.     Lighting.          -         4.00 
Vol.111.  Lighting  Contin'd. 

THERAPEUTICS. 
Allen,  Harlan,  Harte,  Van 

Harlingen.     Local  Thera.   3.00 
Biddle.     13th  Edition  -      4  00 

Field,  Cathartics  and  Emetics.  1.75 
Mays.     Theine.         -         -  .50 

Napheys'  Therapeutics.  Vol. 

1.     Medical  and  Disease  of 

Children.  -  Cloth,  4.00 
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&  Obstet.  -  Cloth,  4.00 

Potter's  Compend.     6th  Ed.       .80 
-,  Handbook  of.  5.00;  Sh.  6.00 


Waring's  Practical.    4th  Ed.  2x0 
White   and    Wilcox.    Mat. 
Med.,  Pharmacy,  Pharmacol- 
ogy, and  Thera.     4th  Ed.      3.00 

THROAT  AND  NOSE. 
Cohen.     Throat  and  Voice.        .40 
Hall.     Nose  and  Throat.    -     2.50 
Hollopeter.     Hay  Fever.         1.00 

Hutchinson.  Nose&Throat. 

Mackenzie.     Throat  Hospital 

Pharmacopoeia.  5th  Ed.  1.00 
McBride.      Clinical  Manual, 

Colored  Plates.  2d  Ed.  -  6.00 
Potter.    Stammering,  etc.         1.00 

URINE  &  URINARY  ORGANS. 
Acton.     Repro.  Organs.  1.75 

Allen.     Diabetic  Urine.  2.25 

Beale.  Urin.  Deposits.  Plates.  2.00 
Holland.  The  Urine,  Milk  and 

Common  Poisons.  5th  Ed.  1.00 
Memminger.     Diagnosis  by 

the  Urine.  2d  Ed.  Illus.  1.00 
Morris.     Renal  Surgery.  2.00 

Moullin.     The  Prostate.    -    

The  Bladder.         -  1.50 


Thompson.  Urinary  Organs.  3.00 
Tyson.  Exam,  of  Urine.  1.25 
Van  Niiys.    Urine  Analysis,     i.co 

VENEREAL  DISEASES. 
Cooper.  Syphilis.  2d  Ed.      -     5.00 
Gowers.      Syphilis  and    the 

Nervous  System.  -  -  1.00 
Jacobson.     Diseases   of  Male 

Organs.     Illustrated.        -       6.00 

VETERINARY. 

Armatage.     Vet.  Rememb.  1.00 

Ballou.     Anat.  and  Phys.  .80 

Tuson.     Pharmacopoeia.  2.25 

VISITING  LISTS. 
Lindsay  &  Blakiston's  Reg- 
ular Edition.  1.00  to  2.25 

Perpetual  Ed.     1.25  to  1.50 

Monthly  Ed.         .75  to  1.00 

Send  /or  Circular. 

WATER. 
LefTmann.    Examination  of.     1.25 
MacDonald.  Examination  of.  2.50 

WOMEN,  DISEASES  OF. 
Byford  (H.  T.).     Manual.   2d 

Edition.  341  Illustrations.  3.00 
Byford  (W.H.).  Text-book.  2.00 
DUhrssen.     Gynecological 

Practice.  105  Illustrations.  1.50 
Lewers.  Dis.  of  Women.  2.50 
Wells.     Compend.     Illus.  .So 


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BLOXAM.  Chemistry,  Inorganic  and  Organic.  With  Experiments.  By 
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King's  College,  London,  and  A.  G.  Bloxam,  Head  of  the  Chemistry  Depart- 
ment, Goldsmiths'  Institute,  London.  Eighth  Edition.  Revised  and  Enlarged. 
281  Engravings,  20  of  which  are  new.     8vo.  Cloth,  $4.25  ;  Leather,  $5.25 

BRACKEN.     Outlines  of  Materia  Medica  and  Pharmacology.     By  H.  M. 

Bracken,  Professor  of  Materia  Medica  and  Therapeutics  and  of  Clinical 
Medicine,  University  of  Minnesota.     8vo.  Cloth,  $2.75 

BROOMELL.    Anatomy  and  Histology  of  the  Human  Mouth  and  Teeth.    By 

Dr.  I.  N.  Broomell,  Professor  ot  Dental  Anatomy,  Dental  Histology,  and 
Prosthetic  Technics  in  the  Pennsylvania  College  of  Dental  Surgery.  With  284 
Handsome  Illustrations,  the  majority  of  which  are  original.     Large  Octavo. 

Cloth,  $4.50 

BROWN.     Medical  Diagnosis.     A  Manual  of  Clinical  Methods.     By  J.  J.  Graham 

Brown,  m.d.,  f.r.c.p.,  Asst.  Physician  Royal  Infirmary;  Lecturer  on  Principles 

and   Practice  of  Medicine  in  the  School  of  Medicine  of  the  Royal  Colleges, 

Edinburgh,  etc.     Fourth  Edition.    112  Illustrations.     i2mo.  Cloth,  $2.25 

BROWN.  Elementary  Physiology  for  Nurses.  By  Miss  Florence  Haig  Brown. 
Late  in  Charge  Nurse  Department,  St.  Thomas'  Hospital,  London.  With  many 
Illustrations.  Cloth,  .75 

BRUBAKER.  Physiology.  A  Compend  of  Physiology,  specially  adapted  for  the 
use  of  Students  and  Physicians.  By  A.  P.  Brubaker,  m.d.,  Adjunct  Professor 
of  Physiology  at  Jefferson  Medical  College,  Prof,  of  Physiology,  Penn'a  College 
of  Dental  Surgery,  Philadelphia.  Ninth  Edition.  Revised,  Enlarged,  and  Illus- 
trated.    No.  4,? Quiz- Compend?  Series.    i2mo.      Cloth,  .80  ;  Interleaved,  $1.25 

BULKLEY.  The  Skin  in  Health  and  Disease.  By  L.  Duncan  Bulkley,  m.d., 
Attending  Physician  at  the  New  York  Hospital.     Illustrated.  Cloth,  .40 

BURNET.  Foods  and  Dietaries.  A  Manual  of  Clinical  Dietetics.  By  R.  W. 
Burnet,  m.d.,  m.r.c.p.,  Physician  to  the  Great  Northern  Central  Hospital. 
With  Appendix  on  Predigested  Foods  and  Invalid  Cookery.  Full  directions  as 
to  hours  of  taking  nourishment,  quantity,  etc.     Second  Edition.  Cloth,  $1.50 

BURNETT.  Hearing,  and  How  to  Keep  It.  By  Chas.  H.  Burnett,  m.d.,  Prof, 
of  Diseases  of  the  Ear  at  the  Philadelphia  Polyclinic.     Illustrated.         Cloth.  .40 

BUXTON.  On  Anesthetics.  A  Manual.  By  Dudley  Wilmot  Buxton,  m.r.c.s., 
m.r.c.p.,  Ass't  to  Prof,  of  Med.,  and  Administrator  of  Anesthetics,  University 
College  Hospital,  London.     Third  Edition,  Illustrated.     i2mo.  In  Press. 


P.  BLAKISTON'S  SON  &-  CO.'S 


BYFORD.  Manual  of  Gynecology.  A  Practical  Student's  Book.  By  Henry  T. 
Byford,  m.d.,  Professor  of  Gynecology  and  Clinical  Gynecology  in  the  College 
of  Physicians  and  Surgeons  of  Chicago ;  Professor  of  Clinical  Gynecology, 
Women's  Medical  School  of  Northwestern  University,  and  in  Post-Graduate 
Medical  School  of  Chicago,  etc.  Second  Edition,  Enlarged.  With  341  Illustra- 
tions, many  of  which  are  from  original  drawings  and  several  of  which  are  col- 
ored.    i2mo.     596  pages.  Cloth,  $3.00 

BYFORD.  Diseases  of  Women.  By  the  late  W.  H.  Byford,  a.m.,  m.d.  Fourth 
Edition.     306  Illustrations.     Octavo.  Cloth,  $2.00 

CALDWELL.  Chemical  Analysis.  Elements  of  Qualitative  and  Quantitative 
Chemical  Analysis.  By  G.  C.  Caldwell,  b.s.,  Ph.D.,  Professor  of  Agricultural 
and  Analytical  Chemistry  in  Cornell  University,  Ithaca,  New  York,  etc.  Third 
Edition.     Revised  and  Enlarged.     Octavo.  Cloth,  $1.50 

CAMERON.  Oils  and  Varnishes.  A  Practical  Handbook,  by  James  Cameron, 
f.i.c.     With  Illustrations,  Formulse,  Tables,  etc.     i2mo.  Cloth,  $2.25 

Soap  and  Candles.     A  New  Handbook   for  Manufacturers,  Chemists,  Ana- 
lysts, etc.     54  Illustrations.     i2mo.  Cloth,  $2.00 

C  ANFIELD.  Hygiene  of  the  Sick-Room.  A  book  for  Nurses  and  others.  Being 
a  Brief  Consideration  of  Asepsis,  Antisepsis,  Disinfection,  Bacteriology,  Immu- 
nity, Heating  and  Ventilation,  and  kindred  subjects,  for  the  use  of  Nurses  and 
other  Intelligent  Women.  By  William  Buckingham  Canfield,  a.m.,  m.d., 
Lecturer  on  Clinical  Medicine  and  Chief  of  Chest  Clinic,  University  of  Mary- 
land, Physician  to  Bay  View  Hospital  and  Union  Protestant  Infirmary,  Balti- 
more.    i2ino.  Cloth,  $1.25 

CARPENTER.  The  Microscope  and  Its  Revelations.  By  W.  B.  Carpenter, 
m.d.,  f.r.s.  Eighth  Edition.  By  Rev.  Dr.  Dallinger,  f.  r.  s.  Revised  and 
Enlarged,  with  800  Illustrations  and  many  Lithographs.     Octavo.        Preparing. 

CAUTLEY.  Feeding  of  Infants  and  Yonng  Children  by  Natural  and  Arti- 
ficial Methods.  By  Edmund  Cautley,  M.d.,  Physician  to  the  Belgrave  Hospital 
for  Children,  London.     121110.  Cloth,  $2.00 

CAZEATJX  and  TARNIER'S  Midwifery.    With  Appendix,  by  Munde.    The 

Theory  and  Practice  of  Obstetrics,  including  the  Diseases  of  Pregnancy  and 
Parturition,  Obstetrical  Operations,  etc.  By  P.  Cazeaux.  Remodeled  and  re- 
arranged, with  revisions  and  additions,  by  S.  Tarnier.m.d.  Eighth  American, 
from  the  Eighth  French  and  First  Italian  Edition.  Edited  by  Robert  J.  Hess, 
m.d.,  Physician  to  the  Northern  Dispensary,  Phila.,  etc.,  with  an  Appendix  by 
Paul  F.  Munde,  m.d.,  Professor  of  Gynecology  at  the  New  York  Polyclinic. 
Illustrated  by  Chromo-Lithographs,  Lithographs,  and  other  Full- page  Plates 
and  numerous  Wood  Engravings.     8vo.  Cloth,  $4.50;  Full  Leather,  $5.50 

COBLENTZ.  Manual  of  Pharmacy.  A  Text-Book  for  Students.  By  Virgil 
Coblentz,  a.m.,  ph.d.,  F.c.s.,  Professor  of  Chemistry  and  Physics;  Director  of 
Pharmaceutical  Laboratory,  College  of  Pharmacy  of  the  City  of  New  York. 
Second  Edition,  Revised  and  Enlarged.    437  Illustrations.    Octavo.     572  pages. 

Cloth,  $3.50;  Sheep,  $4.50  ;  Half  Russia,  $5.50 

The   Newer   Remedies.     Including  their   Synonyms,  Sources,   Methods  of 

Preparation,  Tests,  Solubilities,  and  Doses  as  far  as  known.     Together  with 

Sections  on  Organo-Therapeutic  Agents  and  Indifferent  Compounds  of  Iron. 

Third  Edition,  very  much  enlarged.     Octavo.    Just  Ready.         Cloth,  $1.00 

COHEN.   The  Throat  and  Voice.   By  J.  Solis-Cohen,  m.d.  Illus.   i2mo.   Cloth,  .40 

COLLIE,  On  Fevers.  A  Practical  Treatise  on  Fevers,  Their  History,  Etiology, 
Diagnosis,  Prognosis,  and  Treatment.  By  Alexander  Collie,  m.d.,  m.r.c.p., 
Lond.,  Medical  Officer  of  the  Homerton  and  of  the  London  Fever  Hospitals. 
With  Colored  Plates.     i2mo.  Cloth,  #2.co 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  9 

COOPER.  Syphilis.  By  Alfred  Cooper,  f.r.c.s.,  Senior  Surgeon  to  St.  Mark's 
Hospital ;  late  Surgeon  to  the  London  Lock  Hospital,  etc.  Edited  by  Edward 
Cotterell,  f.r.c.s.,  Surgeon  London  Lock  Hospital,  etc.  Second  Edition. 
Enlarged  and  Illustrated  with  20  Full-Page  Plates  containing  many  handsome 
Colored  Figures.     Octavo.  Cloth,  $5.00 

COPLIN.  Manual  of  Pathology.  Including  Bacteriology,  the  Technic  of  Post- 
Mortems,  and  Methods  of  Pathologic  Research.  By  W.  M.  Late  Coplin,  m  d., 
Professor  of  Pathology  and  Bacteriology,  Jefferson  Medical  College;  Pathologist 
to  Jefferson  Medical  College  Hospital  and  to  the  Philadelphia  Hospital;  Bacte- 
riologist to  the  Pennsylvania  State  Board  of  Health.  Being  the  Second  Edition 
of  the  author's  "Lectures  on  Pathology."  Rewritten  and  Enlarged.  265  Illus- 
trations, many  of  which  are  original.     121110.     638  pages.  Cloth,  $3.00 

COPLIN  and  SEVAN.  Practical  Hygiene.  By  W.  M.  L.  Coplin,  m.d.,  and  D. 
Bevan,  m.d.,  Ass't  Department  of  Hygiene,  Jefferson  Medical  College;  Bac- 
teriologist, St.  Agnes'  Hospital,  Philadelphia,  with  an  Introduction  by  Prof. 
H.  A.  Hare,  and  articles  on  Plumbing,  Ventilation,  etc.,  by  Mr.  W.  P.  Locking- 
ton.     138  Illustrations.     8vo.     Second  Edition.  In  Preparation, 

CRIPPS.  Ovariotomy  and  Abdominal  Surgery.  By  Harrison  Cripps,  f.r.c.s., 
Surgical  Staff,  St.  Bartholomew's  Hospital,  London.  With  17  Plates,  several  01 
which  are  Colored  and  115  other  Illustrations.     Large  Octavo.  Cloth,  $8.00 

CROCKER.  Diseases  of  the  Skin.  Their  Description,  Pathology,  Diagnosis,  and 
Treatment,  with  special  reference  to  the  Skin  Eruptions  of  Children.  By  H. 
Radcliffe  Crocker,  m.d.,  Physician  to  the  Dept.  of  Skin  Diseases,  University 
College  Hospital,  London.     92  Illustrations.     Third  Edition.  Preparing. 

CUFF.  Lectures  on  Medicine  to  Nurses.  By  Herbert  Edmuxd  Cuff,  m.d.,  Late 
Ass't  Medical  Officer,  Stockwell  Fever  Hospital,  England.  Second  Edition,  Re- 
vised.    With  25  Illustrations.  Cloth,  $1.25 

CULLINGWORTH.    A  Manual  of  Nursing,  Medical  and  Surgical.    By  Charles 

J.  Cullingworth,    m.d.,    Physician  to  St.  Thomas'  Hospital,  London.     Third 

Revised  Edition.     With  Illustrations.     i2mo.  Cloth,  .75 

A  Manual  for  Monthly  Nurses.    Third  Edition.    32mo.  Cloth,  .40 

DALBY.  Diseases  and  Injuries  of  the  Ear.  By  Sir  William  B.  Dalby,  m.d., 
Aural  Surgeon  to  St.  George's  Hospital,  London.  Illustrated.  Fourth  Edition. 
With  38  Wood  Engravings  and  8  Colored  Plates.  CJoth,  $2.50 

DAVIS.  A  Manual  of  Obstetrics.  Being  a  complete  manual  for  Physicians  and 
Students.  By  Edward  P.  Davis,  a.m.,  m.d.,  Professor  of  Obstetrics  in  the  Jef- 
ferson Medical  College;  Professor  of  Obstetrics  in  the  Philadelphia  Polyclinic ; 
Clinical  Professor  of  Pediatrics  in  the  Woman's  Medical  College  of  Philadelphia  ; 
Attending  Obstetrician  to  the  Philadelphia  Hospital  and  to  the  Jefferson  Hospital ; 
Member  of  the  American  Gynaecological  Society,  of  the  American  Pediatric 
Society,  of  the  International  Congress  of  Gynaecology  and  Obstetrics,  of  the 
College  of  Physicians  of  Philadelphia,  of  the  Pniladelphia  Obstetrical  Society, 
etc.  Third  Edition,  Revised.  With  many  Colored  and  other  Illustrations,  a 
large  number  of  which  have  been  drawn  for  this  edition  by  a  special  artist. 
l2mo.  Nearly  Ready. 

DAVIS.  Essentials  of  Materia  Medica  and  Prescription  Writing.  By  J. 
Aubrey  Davis,  m.d.,  Ass't  Dem.  of  Obstetrics  and  Quiz  Master  in  Materia 
Medica,  University  of  Pennsylvania;  Ass't  Physician,  Home  for  Crippled  Chil- 
dren, Philadelphia.     i2mo.  $1.50 

DOMVILLE.  Manual  for  Nurses  and  others  engaged  in  attending  to  the  sick.  By 
Ed.  J.  Domville,  m.d.  Eighth  Edition.  Revised.  With  Recipes  for  Sick- 
room Cookery,  etc.     i2mo.  Cloth,  .75 

DONDERS.  Refraction.  An  Essay  on  the  Nature  and  the  Consequences  of 
Anomalies  of  Refraction.  By  F.  C.  Donders,  m.d.,  late  Professor  of  Physiology 
and  Ophthalmology  in  the  University  of  Utrecht.  Authorized  Translation. 
Revised  and  Edited  by  Charles  A.  Oliver,  a.m.,  m.d.  (Univ.  Pa.),  one  of  the 
Attending  Surgeons  to  the  Wills  Eye  Hospital ;  one  of  the  Ophthalmic  Surgeons 
to  the  Pniladelphia  Hospital,  etc.  With  a  very  handsome  Portrait  of  the  Author 
and  a  series  of  Explanatory  Diagrams.     Octavo.     Just  Ready. 

Half  Morocco,  Gilt,  $1.25 


10  P.  BLAKISTON'S  SON  &*  CO.'S 

DEAVER.  Surgical  Anatomy.  A  Treatise  on  Human  Anatomy  in  its  Application 
to  the  Practice  of  Medicine  and  Surgery.  By  John  B.  Deaver,  m.d.,  Assistant 
Professor  of  Applied  Anatomy,  University  of  Pennsylvania ;  Surgeon-in-chief 
to  the  German  Hospital;  Surgeon  to  the  Children's  Hospital,  and  to  the  Phila- 
delphia Hospital ;  Consulting  Surgeon  to  St.  Agnes',  St.  Timothy's,  and  German- 
town  Hospitals,  etc.  With  about  400  very  handsome  full-page  Illustrations 
engraved  from  original  drawings  made  by  special  artists  from  dissections  pre- 
pared for  the  purpose  in  the  dissecting  rooms  of  the  University  of  Pennsylvania. 
Three  large  volumes.  Royal  square  octavo.  Sold'  by  Subscription.  Orders 
taken  for  complete  sets  only. 

Cloth,  $21.00;  Half  Morocco  or  Sheep,  $24.00;  Half  Russia,  $27.00 
Appendicitis.  Its  History,  Anatomy,  Etiology,  Pathology,  Symptoms,  Diag- 
nosis, Prognosis,  Treatment,  Complications,  and  Sequelae.  A  Systematic 
Treatise,  with  Colored  Illustrations  of  Methods  of  Procedure  in  Operating 
and  Plates  of  Typical  Pathological  Conditions  drawn  specially  for  this  work. 
32  Full-Page  Plates.     8vo.  Cloth,  $3.50 

DUCKWORTH.  On  Gout.  Illustrated.  A  treatise  on  Gout.  By  Sir  Dyce 
Duckworth,  m.d.  (Edin.),  f.r.c.p.,  Physician  to,  and  Lecturer  on  Clinical 
Medicine  at,  St.  Bartholomew's  Hospital,  London.  With  Chromo-lithograohs 
and  Engravings.     Octavo.  Cloth,  $6.00 

DUHRSSEN.  A  Manual  of  Gynecological  Practice.  By  Dr.  A.  Duhrssen, 
Privat-docent  in  Midwifery  and  Gynecology  in  the  University  of  Berlin.  Trans- 
lated from  the  Fourth  German  Edition  and  Edited  by  John  W.  Taylor,  f.r.c.s., 
Surgeon  to  the  Birmingham  and  Midlands  Hospital  for  Women;  Vice-President 
of  the  British  Gynecological  Society ;  and  Frederick  Edge,  m.d.,  m.r.c.p., 
f.r.c.s.,  Surgeon  to  the  Wolverhampton  and  District  Hospital  for  Women.  With 
105  Illustrations.     i2mo.  Cloth,  $1.50 

DULLES.  What  to  Do  Eirst  In  Accidents  and  Poisoning.  By  C.  W.  Dulles,  m.d. 
Fifth  Edition,  Enlarged,  with  new  Illustrations.     i2mo.  Cloth.  $1.00 

ECKLEY.  Practical  Anatomy.  A  Manual  for  the  Use  of  Students  in  the  Dissect- 
ing Room.  Based  upon  Morris'  Text-Book  of  Anatomy.  By  W.  T.  Eckley, 
m.d.,  Professor  and  Demonstrator  of  Anatomy  in  the  College  of  Physicians  and 
Surgeons;  Professor  of  Anatomy  in  the  Dental  Department,  Northwestern  Uni- 
versity, Chicago.     With  over  200  Illustrations.     Octavo.  Nearly  Ready. 

FENWICK.  Guide  to  Medical  Diagnosis.  By  Samuel  Fenwick,  m.d.,  f.r.c.p., 
Consulting  Physician  to  the  London  Hospital;  and  W.  S.  Fenwick,  m.d., 
m.r.c.p.,  Physician  to  the  Out-Patients,  Evelina  Hospital  for  Children.  Eighth 
Edition.     In  great  part  rewritten,  with  several  new  chapters.     135  Illustrations. 

Cloth,  $2.50 

FICK.  Diseases  of  the  Eye  and  Ophthalmoscopy.  A  Handbook  for  Physicians 
and  Students.  By  Dr.  Eugen  Fick,  University  of  Zurich.  Authorized  Transla- 
tion by  A.  B.  Hale,  m.d.,  Ophthalmic  Surgeon,  United  Hebrew  Charities  ;  Con- 
sulting Ophthalmic  Surgeon,  Charity  Hospital,  Chicago;  late  Vol.  Assistant, 
Imperial  Eye  Clinic,  University  of  Kiel.  With  a  Glossary  and  158  Illustrations, 
many  of  which  are  in  colors.  8vo.    Cloth,  $4.50 ;  Sheep,  $5.50 ;  Half  Russia,  $6.50 

FIELD.  Evacuant  Medication — Cathartics  and  Emetics.  By  Henry  M.  Field, 
m.d.,  Professor  of  Therapeutics,  Dartmouth  Medical  College,  Corporate  Mem- 
ber Gynaecological  Society  of  Boston,  etc.     i2mo.     288  pp.  Cloth,  $1.75 

FILLEBROWN.  A  Text-Book  of  Operative  Dentistry.  Written  by  invitation 
of  the  National  Association  of  Dental  Faculties.  By  Thomas  Fillebrown,  m.d., 
d.m.d.,  Professor  of  Operative  Dentistry  in  the  Dental  School  of  Harvard  Uni- 
versity ;  Member  of  the  American  Dental  Assoc,  etc.    Illus.    8vo.      Clo.    $2.25 

FOWLER'S  Dictionary  of  Practical  Medicine.  By  Various  Writers.  An  Ency- 
clopedia of  Medicine.  Edited  by  James  Kingston  Fowler,  m.a.,  m.d.,  f.r.c.p., 
Senior  Asst.  Physician  to,  and  Lecturer  on  Pathological  Anatomy  at,  the  Mid- 
dlesex Hospital,  London.     8vo.  Cloth,  $3.00;  Half  Morocco,  $4.00 

GARDNER.    The  Brewer,  Distiller  and  Wine  Manufacturer.    A  Handbook  for 

all  Interested  in  the  Manufacture  and  Trade  of  Alcohol  and  Its  Compounds. 

Edited  by  John  Gardner,  f.c.s.     Illustrated.  Cloth,  $1.50 

Bleaching,  Dyeing,  and  Calico  Printing.  With  Formulae.    Illustrated.     $1.50 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  11 

FTJLLERTON.  Obstetric  Nursing.  By  Anna  M.  Fullerton,  m.d.,  Demon- 
strator of  Obstetrics  in  the  Woman's  Medical  College ;  Physician  in  charge 
of,  and  Obstetrician  and  Gynecologist  to,  the  Woman's  Hospital,  Philadelphia, 
etc.  41  Illustrations.    Fifth  Edition.    Revised  and  Enlarged.   i2mo.     Cloth,  $1.00 

Nursing  in  Abdominal  Surgery  and  Diseases  of  Women.  Comprising  the 
Regular  Course  of  Instruction  at  the  Training  School  of  the  Woman's 
Hospital,  Philadelphia.    Second  Ed.     70  Illustrations.     i2mo.     Cloth,  $1.50 

G  A.RK.0D.  On  Rheumatism.  A  Treatise  on  Rheumatism  and  Rheumatic  Arthritis. 
By  Archibald  Edward  Garrod,  m.a.  (Oxon.),  m.d.,  m.r.c.s.  (Eng.),  Asst. 
Physician,  West  London  Hospital.     Illustrated.     Octavo.  Cloth,  $5.00 

GILLIAM'S  Pathology.  The  Essentials  of  Pathology ;  a  Handbook  for  Students. 
By  D.  Tod  Gilliam,  m.d.,  Professor  of  Physiology,  Starling  Medical  College, 
Columbus,  O.    With  47  Illustrations.    i2mo.  Cloth,  .75 

GOODALL  and  WASHBOURN.  A  Manual  of  Infectious  Diseases.  By 
Edward  W.  Goodall,  m.d.  (London),  Medical  Superintendent  Eastern  (Fever) 
Hospital,  Homerton,  London,  etc.,  and  J.  W.  Washbourn,  f.r.c.p.,  Assistant 
Physician  to  Guy's  Hospital  and  Physician  to  the  London  Fever  Hospital. 
Illustrated  with  Charts,  Diagrams,  and  Full-Page  Plates.  Cloth,  $3.00 

GORGAS'S  Dental  Medicine.  A  Manual  of  Materia  Medica  and  Therapeutics. 
By  Ferdinand  J.  S.  Gorgas,  m.d.,  d.d.s.,  Professor  of  the  Principles  of  Dental 
Science,  Oral  Surgery  and  Dental  Mechanism  in  the  Dental  Dep.  of  the  Univ. 
of  Maryland.    Sixth  Edition.    Revised  and  Enlarged,  with  many  Formulae.    8vo. 

Cloth,  $4.00;  Sheep,  $5.00;  Half  Russia,  $6.00 

GOULD.    The  Illustrated  Dictionary  of  Medicine,  Biology,  and  Allied  Sciences. 

Being  an  Exhaustive  Lexicon  of  Medicine  and  those  Sciences  Collateral  to  it : 
Biology  (Zoology  and  Botany),  Chemistry,  Dentistry,  Pharmacology,  Microscopy, 
etc.     By  George  M.  Gould,  m.d.,  Editor  of  The  Philadelphia  Medical  Journal  ; 
President,  1893-94,  American  Academy  of  Medicine,  etc.     With  many  Useful 
Tables  and  numerous  Fine  Illustrations.     Large,  Square  Octavo.     1633  pages. 
Fourth  Edition  now  Ready.     Full  Sheep,  or  Half  Dark-Green  Leather,  $10.00; 
With  Thumb  Index,  $11.00;  Half  Russia,  Thumb  Index,  $12.00 
The  .Student's  Medical  Dictionary.   Tenth  Edition.    Enlarged.   Including 
all  the  Words  and  Phrases  generally  used  in  Medicine,  with  their  proper 
Pronunciation  and  Definitions,  based  on  Recent  Medical  Literature.     With 
Tables  of  the  Bacilli,  Micrococci,  Leucomains,  Ptomains,  etc.,  of  the  Arteries, 
Muscles,  Nerves,  Ganglia  and  Plexuses;  Mineral  Springs  of  U.  S.,  etc.    Re- 
written, Enlarged,  and  set  from  new  Type.     Small  octavo,  700  pages. 

Half  Dark  Leather,  $3.25;  Half  Morocco,  Thumb  Index,  $4.co 

The  Pocket  Pronouncing  Medical  Lexicon.  (21,000  Medical  Words 
Pronounced  and  Defined.)  A  Student's  Pronouncing  Medical  Lexicon. 
Containing  all  the  Words,  their  Definition  and  Pronunciation,  that  the 
Student  generally  comes  in  contact  with;  also  elaborate  Tables  of  the 
Arteries,  Muscles,  Nerves,  Bacilli,  etc.,  etc.;  a  Dose  List  in  both  English 
and  Metric  Systems,  a  new  table  of  Clinical  Eponymic  Terms,  etc., 
arranged  in  a  most  convenient  form  for  reference  and  memorizing.  A  new 
edition,  completely  revised  and  set  from  new  type.  200  pages  new  material. 
Thin  64tno.  (6x3^  inches.)  The  System  of  Pronunciation  used  in  this  book 
is  very  simple.  Full  Limp  Leather,  Gilt  Edges,  $1.00;  Thumb  Index,  $1.25 
***  Sample  pages  and  descriptive  circulars  sent  free  upon  application.    See  page  4 

Borderland  Studies.  Miscellaneous  Addresses  and  Essays  Pertaining  to  Medi- 
cine and  the  Medical  Profession,  and  Their  Relations  to  General  Science 
and  Thought.    By  George  M.  Gould,  m.d.    350  pages,    nmo,    Cloth,  $2.00 

Compend  of  Diseases  of  the  Eye  and  Refraction.  Including  Treatment 
and  Operations,  with  a  Section  on  Local  Therapeutics.  By  George  M. 
Gould,  m.d.,  and  W.  L.  Pyle,  m.d.  With  Formulae,  Glossary,  and  several 
Tables.  111  Illustrations,  several  of  which  are  Colored.  Being  No.  8 
f  Quiz- Compend?  Series.  Cloth,  .80.     Interleaved  for  Notes,  $1.25 


12  P.  BLAKISTON'S  SON  6-  CO.'S 

GORDINIER.  The  Gross  and  Minute  Anatomy  of  the  Central  Nervous 
System.  By  H.  C.  GORDINIER,  a.m.,  m.d.,  Prolessor  of  Physiology  and  of  the 
Anatomy  of  the  Nervous  System  in  the  Albany  Medical  College.  With  many 
full-page  Plates  and  other  Illustrations,  a  number  of  which  are  printed  in  colors 
and  the  majority  of  which  are  original.     Large  Octavo. 

Handsome  Cloth,  $6.00;  Sheep,  $7.00;  Half  Russia,  $8.00 

GRIFFITH'S  Graphic  Clinical  Chart.  Designed  by  J.  P.  Crozer  Griffith, 
m.d.,  Instructor  in  Clinical  Medicine  in  the  University  of  Pennsylvania.  Printed 
in  three  colors.     Sample  copies  free.  Put  up  in  loose  packages  of  50,    .50 

Price  to  Hospitals,  500  copies,  $4.00;   1000  copies,  $7.50.     With  name  of  Hos- 
pital printed  on,  50  cents  extra. 

GROFF.  Materia  Medica  for  Nurses.  With  Questions  for  Self-Examination 
and  a  very  complete  Pronouncing  Glossary.  By  John  E.  Groff,  Pharmacist 
Rhode  Island  Hospital,  Providence.     i2mo.     235  pages.  Cloth,  $1.25 

GROVES  and  THORP.  Chemical  Technology.  A  new  and  Complete  Work. 
The  Application  of  Chemistry  to  the  Arts  and  Manufactures.  Edited  by 
Charles  E.  Groves,  f.r.s.,  and  Wm.  Thorp,  b.Sc,  f.i.c,  assisted  by  many 
experts.  In  about  eight  volumes,  with  numerous  illustrations.  Each  volume 
sold  separately. 

Vol.  I.   Fuel  and  Its  Applications.    607  Illustrations  and  4  Plates.    Octavo. 

Cloth,  $5.00;  Half  Morocco,  $6.50 
Vol.11.  Lighting.  Illustrated.  Octavo.  Cloth,  $4.00;  Half  Morocco,  $5. 50 
Vol.  III.     Lighting — Continued.  In  Press. 

GOWERS.  Manual  of  Diseases  of  the  Nervous  System.  A  Complete  Text-book. 
By  William  R.  Gowers,  m.d.,  f.r.s.,  Physician  to  National  Hospital  for  the 
Paralyzed  and  Epileptic;  Consulting  Physician,  University  College  Hospital; 
formeily  Professor  of  Clinical  Medicine,  University  College,  etc.  Second 
Edition.  With  many  new  Illustrations.  Two  Volumes.  Octavo. 
Vol.  I.    Diseases  of  the  Nerves  and  Spinal  Cord.    616  pages. 

Cloth,  $3.00  ;  Sheep,  $4.00;  Half  Russia,  $5.00 

Vol.  II.    Brain  and  Cranial  Nerves ;  General  and  Functional  Diseases. 

1069  pages.  Cloth,  $4.00  ;  Sheep,  $5.00;  Half  Russia,  $6.00 

*V*This  book  has  been  translated  into  German,  Italian,  and  Spanish.      It  is 
published  in  London,  Milan,  Bonn,  Barcelona,  and  Philadelphia. 

Syphilis  and  the  Nervous  System.    Being  a  revised  reprint  of  the  Lettso- 

mian  Lectures  for  1890,  delivered  before  the  Medical  Society  of  London. 

121110.  Clo:h,$i.oo 

Diagnosis  of  Diseases  of  the  Brain.    8vo.    Second  Ed.    Illus.    Cloth,  $1.50 
Medical  Ophthalmoscopy.    A  Manual  and  Atlas,  with  Colored  Autotype  and 

Lithographic  Plates  and  Wood-cuts,  comprising  Original  Illustrations  of  the 

changes  of  the  Eye  in  Diseases  of  the  Brain,  Kidney,  etc.     Third  Edition. 

Revised,  with  the  assistance  of  R.  Marcus  Gunn,  f.r.c.s.,  Surgeon,  Royal 

London  Ophthalmic  Hospital,  Moorfields.     Octavo.  Cloth,  #4.00 

The  Dynamics  of  Life.    nmo.  Cloth,  .75 

Clinical  Lectures.     A  new  volume  of  Essays  on  the  Diagnosis,  Treatment, 

etc.,  of  Diseases  of  the  Nervous  System.  Cloth,  $2.00 

Epilepsy  and  Other  Chronic  Convulsive  Diseases.  Second  Edition,  hi  Press 

HAIG.  Causation  of  Disease  by  Uric  Acid.  A  Contribution  to  the  Pathology  of 
High  Arterial  Tension,  Headache,  Epilepsy,  Mental  Depression,  Gout,  Rheu- 
matism, Diabetes,  Bright's  Disease,  Anaemia,  etc.  By  Alex.  Haig,  m.a.,  m.d. 
(Oxon.),  f.r.c  p.,  Physician  to  Metropolitan  Hospital,  London.  65  Illustrations. 
Fourth  Edition.  Cloth,  $3.00 

Diet  and  Food.     Considered  in  relation  to  Strength  and  Power  of  Endurance. 

Cloth,  $1.00 

HALE.    On  the  Management  of  Children  in  Health  and  Disease.       Cloth,  .50 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  13 

HALL.  Compend  of  General  Pathology  and  Morbid  Anatomy.  ByH.Newbery 
Hall,  ph.g.,  m.d.,  Professor  of  Pathology,  Post-Graduate  Medical  School, 
Chicago.     91  Illus.     2d  Edition.     No.  15  ? Quiz- Compend?  Series.       Preparing. 

HALL.  Diseases  of  the  Nose  and  Throat.  By  F.  De  Havilland  Hall,  m.d., 
f.r.c.p.  (Lond.),  Physician  in  charge  Throat  Department  Westminster  Hospital; 
Joint  Lecturer  on  Principles  and  Practice  of  Medicine,  Westminster  Hospital 
Medical  School,  etc.     Two  Colored  Plates  and  59  lllus.     i2mo.  Cloth,  $2.50 

HAMILTON.  Lectures  on  Tumors  from  a  Clinical  Standpoint.  By  John  B. 
Hamilton,  m.d.,  ll.d.,  Professor  of  Surgery  in  Rush  Medical  College,  Chicago  ; 
Professor  of  Surgery,  Chicago  Polyclinic  ;  Surgeon  Presbyterian  Hospital,  etc. 
Third  Edition,  Revised  with  new  Illustrations.     i2mo.  Cloth,  $1.25 

HANSELL  and  BEBEB.  Muscular  Anomalies  of  the  Eye.  By  Howard  F. 
Hansell,  a.m.,  m.d.,  Clinical  Piofessor  of  Ophthalmology,  Jefferson  Medical 
College;  Professor  of  Diseases  of  the  Eye,  Philadelphia  Polyclinic,  etc.,  and 
Wendell  Reber,  m.d.,  Instructor  in  Ophthalmology,  Philadelphia  Polyclinic, 
etc.     With  1  Plate  and  28  other  Illustrations.     i2mo.  Cloth,  $1.50 

HANSELL  and  BELL.  Clinical  Ophthalmology.  By  Howard  F.  Hansell, 
a.m.,  m.d.,  and  James  H.  Bell,  m.d.  With  Colored  Plate  of  Normal  Fundus 
and  120  Illustrations.     i2mo.  Cloth,  $1.50 

HABE.  Mediastinal  Disease.  The  Pathology,  Clinical  History  and  Diagnosis  of 
Affections  of  the  Mediastinum  other  than  those  of  the  Heart  and  Aorta.  By  H.  A. 
Hare,  m.d.,  Professor  of  Materia  Medica  and  Therapeutics  in  Jefferson  Medical 
College,  Philadelphia.     8vo.     Illustrated  by  Six  Plates.  Cloth,  $2.00 

HABLAN.    Eyesight,  and  How  to  Care  for  It.    By  George  C.  Harlan,  m.d., 
Prof,  of  Diseases  of  the  Eye,  Philadelphia  Polyclinic.     Illustrated.         Cloth,  .40 
HABBIS'S  Principles  and  Practice  of  Dentistry.    Including  Anatomy,  Physi- 
ology, Pathology,  Therapeutics,  Dental  Surgery  and  Mechanism.     By  Chapin  A. 
Harris,  m.d.,  d.d.s.,  late  President  of  the  Baltimore  Dental  College,  Author  of 
"  Dictionary  of  Medical  Terminology  and  Dental  Surgery."     Thirteenth  Edition. 
Revised  and  Edited  by  Ferdinand  J.  S.  Gorgas,  a.m.,  m.d.,  d.d.s.,  Author  of 
"Dental    Medicine;"     Professor    of    the  Principles   of   Dental   Science,    Oral 
Surgery,  and  Dental  Mechanism  in  the  University  of  Maryland.     1250  Illustra- 
tions.   1 1 80  pages.     8vo.  Cloth,  $6.00;  Leather,  $7.00 ;  Half  Russia,  $8.00 
Dictionary  of  Dentistry.     Including  Definitions  of  such  Words  and  Phrases 
of  the  Collateral  Sciences  as  Pertain  to  the  Art  and  Practice  of  Dentistry. 
Sixth  Edition.     Rewritten,  Revised  and   Enlarged.     By  Ferdinand  J.  S. 
Gorgas,  m.d.,  d.d.s.,  Author  of  "Dental  Medicine;"    Editor  of  Harris's 
"Principles  and  Practice  of  Dentistry;"  Professor  of  Principles  of  Dental 
Science,  Oral  Surgery,  and  Prosthetic  Dentistry  in  the  University  of  Mary- 
land.    Octavo.  Cloth,  $5.00  ;  Leather,  $6.00 

HABBIS  and  BEALE.  Treatment  of  Pulmonary  Consumption.  By  Vincent 
Dormer  Harris,  m.d.  (Lond.),  f.r.c.p.,  Physician  to  the  city  of  London  Hospi- 
tal for  Diseases  of  the  Chest;  Examining  Physician  to  the  Royal  National  Hos- 
pital for  Diseases  of  the  Chest,  Ventnor,  etc.,  and  E.  Clifford  Beale,  m.a., 
m.b.  (Cantab.),  f.r.c.p.,  Physician  to  the  City  of  London  Hospital  for  Diseases 
of  the  Chest,  etc.     121110.  Cloth,  $2.50 

HABTBIDGE.  Befraction.  The  Refraction  of  the  Eye.  A  Manual  for  Students. 
By  Gustavus  Hartridge,  f.r.c.S.,  Consulting  Ophthalmic  Surgeon  to  St.  Bar- 
tholomew's Hospital,  etc.  104  Illustrations  and  Sheet  of  Test  Types.  Ninth 
Edition.     Revised  and  Enlarged  by  the  Author.  Cloth,  $1.50 

On  The  Ophthalmoscope.  A  Manual  for  Physicians  and  Students.  Third 
Edition.     With  Colored  Plates  and  68  Wood-cuts.     i2mo.  Cloth,  $1.50 

HABTSHOBNE.  Our  Homes.  Their  Situation,  Construction,  Drainage,  etc.  By 
Henry  Hartshorne,  m.d.     Illustrated.  Cloth,  .40 

HATFIELD.  Diseases  of  Children.  By  Marcus  P.  Hatfield,  Professor  of 
Diseases  of  Children,  Chicago  Medical  College.  With  a  Colored  Plate.  Second 
Edition.     Being  No.  14,  ?  Quiz- Compend  ?  Series.     i2mo.  Cloth,  .80 

Interleaved  for  the  addition  of  notes,  $1.25 


14  P.  BLAKISTON'S  SON  &*  CO.'S 

HELLER.  Essentials  of  Materia  Medica,  Pharmacy,  and  Prescription  Writ- 
ing. By  Edwin  A.  Heller,  m.d.,  Quiz-Master  in  Materia  Medica  and  Phar- 
macy at  the  Medical  Institute,  University  of  Pennsylvania.     i2mo.    Cloth,  $1.50 

HEATH.    Minor  Surgery  and  Bandaging.    By  Christopher  Heath,  f.r.c.s., 

Holme   Professor  of  Clinical   Surgery   in   University  College,  London.     Tenth 

Edition.      Revised  and   Enlarged.     With   158    Illustrations,  62  Formulae,  Diet 

List,  etc.     i2mo.  Cloth,  $1.25 

Practical  Anatomy.      A  Manual  of  Dissections.      Eighth  London  Edition. 

300  Illustrations.  Cloth,  $4.25 

Injuries  and  Diseases  of  the  Jaws.    Fourth  Edition.    Edited  by  Henry 

Percy   Dean,    m.s.,  f.r.c.s.,  Assistant   Surgeon    London  Hospital.     With 

187  Illustrations.    8vo.  Cloth,  $4.50 

Lectures  on  Certain  Diseases  of  the  Jaws,  delivered  at  the  Royal  College  of 

Surgeons  of  England,  1887.     64  Illustrations.     8vo.  Boards,  .50 

HEMMETER,  Diseases  of  the  Stomach.  Their  Special  Pathology,  Diagnosis, 
and  Treatment.  With  Sections  on  Anatomy,  Analysis  of  Stomach  Contents, 
Dietetics,  Surgery  of  the  Stomach,  etc.  By  John  C.  Hemmeter,  m.d.,  philos.d., 
Clinical  Professor  of  Medicine  in  the  University  of  Maryland  ;  Consultant  to  the 
University  Hospital ;  Director  of  the  Clinical  Laboratory,  etc.;  formerly  Clini- 
cal Professor  of  Medicine  at  the  Baltimore  Medical  College,  etc.  With  Colored 
and  other  Illustrations.  Cloth,  $6.00 ;  Leather,  $7.00;  Half  Russia,  $8.00 

HENRY.  Anaemia.  A  Practical  Treatise.  By  Fred'k  P.  Henry,  m.d.,  Physician 
to  Episcopal  Hospital,  Philadelphia.  Half  Cloth,  .50 

HEWLETT.  Manual  of  Bacteriology.  By  R.  T.  Hewlett,  m.d.,  m.r.c.p.,  Asst. 
Bacteriologist  British  Institute  of  Preventive  Medicine,  etc.  With  75  Illustra- 
tions.    Octavo.  Cloth,  $3.00 

HOLLOPETER.  Hay  Fever  and  Its  Successful  Treatment.  By  W.  C.  Hollo- 
peter,  a.m.,  m.d.,  Clinical  Professor  of  Pediatrics  in  the  Medico  Chirurgical  Col- 
lege of  Philadelphia,  Physician  to  the  Methodist  Episcopal,  Medico-Chirurgical, 
and  St.  Joseph  Hospitals,  etc.     i2mo.  Cloth,  $1.00 

HOLDER'S  Anatomy.  Seventh  Edition.  A  Manual  of  the  Dissections  of  the  Human 
Body.  By  John  Langton,  f.r.c.s.,  Surgeon  to,  and  Lecturer  on  Anatomy  at, 
St.  Bartholomew's  Hospital.  Carefully  Revised  by  A.  Hewson,  m.d.,  Demonstra- 
tor of  Anatomy,  Jefferson  Medical  College,  etc.  311  Illustrations.  i2mo.  800 
pages.  Preparing. 

Human  Osteology.  Comprising  a  Description  of  the  Bones,  with  Colored 
Delineations  of  the  Attachments  of  the  Muscles.  The  General  and  Micro- 
scopical Structure  of  Bone  and  its  Development.  8th  Ed.,  carefully  Revised. 
With  Lithographic  Plates  and  Numerous  Illustrations.  Cloth,  $5.25 

Landmarks.     Medical  and  Surgical.     4th  Edition.     8vo.  Cloth,  $1.00 

HOLLAND.  The  Urine,  the  Gastric  Contents,  the  Common  Poisons  and  the 
Milk.  Memoranda,  Chemical  and  Microscopical,  for  Laboratory  Use.  By  J.  W. 
Holland,  m.d.,  Professor  of  Medical  Chemistry  and  Toxicology  in  Jefferson 
Medical  College,  of  Philadelphia.  Fifth  Edition,  Enlarged.  Illustrated  and 
Interleaved.  i2mo.  Cloth, $1.00 

HORWITZ'S  Compend  of  Surgery,  including  Minor  Surgery,  Amputations,  Frac- 
tures, Dislocations,  Surgical  Diseases,  and  the  Latest  Antiseptic  Rules,  etc.,  with 
Differential  Diagnosis  and  Treatment.  By  Orville  Horwitz,  b.s.,  m.d.,  Pro- 
fessor of  Genito-Urinary  Diseases,  late  Demonstrator  of  Surgery,  Jefferson  Medi- 
cal College.  Fifth  Edition.  Very  much  Enlarged  and  Rearranged.  Over  300 
pages.     167  Illustrations  and  98  Formulae.    i2mo.  No.  9  ? Quiz- Compend?  Series. 

Cloth,  .80.     Interleaved  for  notes,  $1.25 
***  A  Spanish  translation  of  this  book  has  recently  been  published  in  Barcelofia. 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  15 

HORSLEY.  The  Brain  and  Spinal  Cord.  The  Structure  and  Functions  of.  By 
Victor  A.  Horsley,  m.b.,  f.r.s.,  etc.,  Asst.  Surg.,  University  College  Hospital, 
London,  etc.     Illustrated.  Cloth,  $2.50 

HOVELL.  Diseases  of  the  Ear  and  Naso-Pharynx.  A  Treatise  including 
Anatomy  and  Physiology  of  the  Organ,  together  with  the  treatment  of  the  affec- 
tions of  the  Nose  and  Pharynx  which  conduce  to  aural  disease.  By  T.  Mark 
Hovell,  f.k.c.s.  (Edin.),  m.r.c.s.  (Eng.),  Aural  Surgeon  to  the  London  Hospital, 
for  Diseases  of  the  Throat,  etc.      122  Illus.     Second  Edition.  Preparing. 

HUMPHREY.  A  Manual  for  Nurses.  Including  general  Anatomy  and  Physiology, 
management  of  the  sick-room,  etc.  By  Laurence  Humphrey,  m.a.,  m.b., 
m.r.c.s.,  Assistant  Physician  to,  and  Lecturer  at,  Addenbrook's  Hospital,  Cam- 
bridge, England.     Sixteenth  Edition.     i2mo.     Illustrated.  Cloth,  $1.00 

HUGHES.  Compend  of  the  Practice  of  Medicine.  Sixth  Edition.  Revised  and 
Enlarged.  By  Daniel  E.  Hughes,  m.d.,  Chief  Resident  Physician  Philadelphia 
Hospital ;  formerly  Demonstrator  of  Clinical  Medicine  at  Jefferson  Medical  Col- 
lege, Philadelphia.  In  two  parts.  Being  Nos.  2  and 3,  ? Quiz- Compend?  Series. 
Part  I. — Continued,  Eruptive  and  Periodical  Fevers,  Diseases  of  the  Mouth, 
Stomach,  Intestines,  Peritoneum,  Biliary  Passages,  Liver,  Kidneys,  Blood,  etc., 
Parasites,  etc.,  and  General  Diseases,  etc. 

Part  II. — Physical  Diagnosis,  Diseases  of  the  Respiratory  System,  Circulatory 
System,  Diseases  of  the  Brain  and  Nervous  System,  Mental  Diseases,  etc. 

Price  of  each  Part,  in  Cloth,  .80 ;  interleaved  for  the  addition  of  Notes,  $1.25 
Physicians'  Edition. — In  one  volume,  including  the  above  two  parts,  a  sec- 
tion on  Skin  Diseases,  and  an  index.      Sixth  revised,  enlarged  Edition. 
568  pages.  Full  Morocco,  Gilt  Edge,  $2.25 

"  Carefully  and  systematically  compiled." — The  London  Lancet. 

HUTCHINSON.  The  Nose  and  Throat.  A  Manual  of  the  Diseases  of  the  Nose 
and  Throat,  including  the  Nose,  Naso-Pharynx,  Pharynx  and  Larynx.  By 
Procter  S.  Hutchinson,  m.r.c.s.,  Ass't  Surgeon  to  the  London  Hospital  for 
Diseases  of  the  Throat.  Illustrated  by  Lithograph  Plates  and  40  other  Illus., 
many  of  which  have  been  made  from  original  drawings.    i2ino.    2d  Ed.    In  Press. 

IMPEY.  A  Handbook  on  Leprosy.  By  S.  P.  Impey,  m.d.,  m.c,  Late  Chief  and 
Medical  Superintendent,  Robben  Island  Leper  and  Lunatic  Asylums,  Cape  Col- 
ony, South  Africa.     Illustrated  by  37  Plates  and  a  Map.     Octavo.      Cloth,  $3.50 

JACOBSON.     Operations  of  Surgery.     By  W.  H.  A.  Jacobson,  b.a.  (Oxon.), 

f.r  c.s.,  (Eng.);  Ass't  Surgeon,  Guy's  Hospital;    Surgeon  at  Royal  Hospital  for 

Children  and  Women,  etc.     With  over  200  Illust.      Cloth,  $3.00  ;  Leather,  $4.00 

Diseases  of  the  Male  Organs  of  Generation.    88  Illustrations.    Cloth,  $6.00 

JESSOP.  Manual  of  Ophthalmic  Surgery  and  Medicine.  By  Walter  H.  H. 
Jessop,  m.b.  (Cantab.),  F.R. c.s.,  Ophthalmic  Surgeon  to  and  Lecturer  on  Oph- 
thalmic, Medicine  and  Surgery  at  St.  Bartholomew's  Hospital,  London.  With 
5  Colored  Plates,  Test  Types,  and  no  other  Illustrations.     i2mo.       Cloth,  $3.00 

JONES.  Medical  Electricity.  A  Practical  Handbook  for  Students  and  Prac- 
titioners of  Medicine.  By  H.  Lewis  Jones,  m.a.,  m.d.,  m.r.c.p.,  Medical  Officer 
in  Charge  Electrical  Department,  St.  Bartholomew's  Hospital.  Thud  Edition 
of  Steavenson  and  Jones'  Medical  Electricity.  Revised  and  Enlarged.  112  Illus- 
trations.    i2mo.  Preparing. 

KEEN.  Clinical  Charts.  A  series  of  seven  Outline  Drawings  of  the  Human  Body, 
on  which  may  be  marked  the  course  of  any  Disease,  Fractures,  Operations,  etc. 
By  W.  W.  Keen,  m.d.,  Professor  of  the  Principles  of  Surgery  and  Clinical  Sur- 
gery, Jefferson  Medical  College,  Philadelphia.  Put  up  in  pads  of  50,  with 
explanations.  Each  pad,  $1.00.  Each  Drawing  may  also  be  had  separately 
gummed  on  back  for  pasting  in  case  book.     25  to  the  pad.     Price,  25  cents. 

***  Special  Charts  will  be  printed  to  order.     Samples  free. 


16  P.  BLAKISTON'S  SON  &*  CO.'S 

KIRKE'S  Physiology.  ['jM  Authorised  Edition.  121110.  Dark  Red  Cloth.) 
A  Handbook  of  Physiology.  Fourteenth  London  Edition,  Revised  and  Enlarged. 
By  W.  D.  Halliburton,  m.d.,  f.r.s.,  Professor  of  Physiology  King's  College, 
London.  Thoroughly  Revised  and  in  many  parts  Rewritten.  668  lllus.,  many 
of  which  are  printed  in  Colors.    872  pages.     i2mo.    Cloth,  $3.00;   Leather,  $375 

IMPORTANT   NOTICE.     This  >s  tne  identical  Edition  of  "  Kirke's  Physiology,"  as  published 

in   London  by  John   Murray,  the  sole  owner  of  the  book.     It  is  the 

only  edition  containing  the  revisions  and  additions  of  Dr.  Halliburton,  and  the  new  and  original 
illustrations  included  at  his  suggestion.  It  is  the  edition  of  which  the  London  I4ancet  says: 
"The  book  as  now  presented  to  the  student  may  be  regarded  as  a  thoroughly  reliable  exposition 
of  the  present  state  of  physiological  science." 

KENWOOD.  Public  Health  Laboratory  Work.  By  H.  R.  Kenwood,  m.b., 
d.p.h.,  F.c.s.,  Instructor  in  Hygienic  Laboratory,  University  College,  late  Assistant 
Examiner  in  Hygiene,  Science  and  Art  Department,  South  Kensington,  London, 
etc.     With  1 16  Illustrations  and  3  Plates.  Cloth,  $2.00 

KLEEN.  Handbook  of  Massage.  By  Emil  Kleen,  m.d.,  ph.d.,  Stockholm  and 
Carlsbad.  Authorized  Translation  from  the  Swedish,  by  Edward  Mussey  Hart- 
well,  m.d.,  PH.D.,  Director  of  Physical  Training  in  the  Public  Schools  of  Boston. 
With  an  Introduction  by  Dr.  S.  Weir  Mitchell,  of  Philadelphia.  Illustrated 
by  Photographs  made  specially  for  the  American  Edition.     8vo.         Cloth,  $2.25 

LANDIS'  Compend  of  Obstetrics  ;  especially  adapted  to  the  Use  of  Students  and 
Physicians.  By  Henry  G.  Landis,  m.d.  Sixth  Edition.  Revised  by  Wm.  H. 
Wells,  m.d.,  Instructor  of  Obstetrics,  Jefferson  Medical  College;  Member 
Obstetrical  Society  of  Philadelphia,  etc.  With  47  Illustrations.  No.  5  fQuiz- 
Compend?  Series.  Cloth,  .80;  interleaved  for  the  addition  of  Notes,  $1.25 

LANDOIS.  A  Text-Book  of  Human  Physiology  ;  including  Histology  and  Micro- 
scopical Anatomy,  with  special  reference  to  the  requirements  of  Practical  Medi- 
cine. By  Dr.  L.  Landois,  Professor  of  Physiology  and  Director  of  the  Physio- 
logical Institute  in  the  University  of  Greifswald.  Fifth  American,  translated 
from  the  last  German  Edition,  with  additions,  by  Wm.  Stirling,  m.d.,  d.Sc, 
Brackenbury  Professor  of  Physiology  and  Histology  in  Owen's  College,  and  Pro- 
fessor in  Victoria  University,  Manchester  ;  Examiner  in  Physiology  in  University 
of  Oxford,  England.  With  845  Illustrations,  many  of  which  are  printed  in 
Colors.     8vo.  In  Press. 

LANE.  Surgery  of  the  Head  and  Neck.  By  L.  C.  Lane,  a.m.,  m.d.,  m.r.c.s. 
(Eng.),  Professor  of  Surgery  in  Cooper  Medical  College,  San  Francisco.  Second 
Edition,  with  no  Illustrations.     Octavo.  Cloth,  $5.00 

LAZARUS-BARLOW.    General  Pathology.    By  W.  S.  Lazarus-Barlow,  m.d., 
Demonstrator  of  Pathology  at  the  University  of  Cambridge,  England. 
795  pages.     Octavo.  Cloth,  $5.00 

LEE.  The  Microtomist's  Vade  Mecum.  Fourth  Edition.  A  Handbook  of 
Methods  of  Microscopic  Anatomy.  By  Arthur  Bolles  Lee,  formerly  Ass't  in 
the  Russian  Laboratory  of  Zoology,  at  Villefranche-sur-Mer  (Nice).  887  Articles. 
Enlarged  and  Revised,  and  in  many  portions  greatly  extended.    8vo.   Cloth,  $4.00 

LEFFMANN'S  Compend  of  Medical  Chemistry,  Inorganic  and  Organic.  In- 
cluding Urine  Analysis.  By  Henry  Leffmann,  m.d.,  Prof,  of  Chemistry  in 
the  Woman's  Medical  College  in  the  Penna.  College  of  Dental  Surgery  and 
in  the  Wagner  Free  Institute  of  Science,  Philadelphia  ;  Pathological  Chemist 
Jefferson  Medical  College.  No.  10  f  Quiz- Compend?  Series.  Fourth  Edition. 
Rewritten.  Cloth,  .80.    Interleaved  for  the  addition  of  Notes,  $1.25 

The  Coal-Tar  Colors,  with  Special  Reference  to  their  Injurious  Qualities  and 
the  Restrictions  of  their  Use.  A  Translation  of  Theodore  Weyl's  Mono- 
graph.    i2mo.  Cloth,  $1.25 

Examination  of  Water  for  Sanitary  and  Technical  Purposes.  Third  Edition. 
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Analysis  of  Milk  and  Milk  Products.  Arranged  to  suit  the  needs  of  Analyt- 
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and  Enlarged,  with  Illustrations.     i2mo.  Cloth,  $1.25 

Handbook  of  Structural  Formulae  for  the  Use  of  Students,  containing  180 
Structural  and  Stereochemic  Formulae.     121110.    Interleaved.     Cloth,  $1.00 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  17 


LEFFMANN  and  BEAM.    Select  Methods  in  Food  Analysis.      In  Preparation. 

LEWERS.  On  the  Diseases  of  Women.  A  Practical  Treatise.  By  Dr.  A.  H. 
N.  LEWERS,  Assistant  Obstetric  Physician  to  the  London  Hospital ;  and  Phy- 
sician to  Out-patients,  Queen  Charlotte's  Lying-in  Hospital;  Examiner  in  Mid- 
wifery and  Diseases  of  Women  to  the  Society  of  Apothecaries  of  London.  With 
146  Engravings.     Fifth  Edition,  Revised.  Cloth,  $2.50 

LEWIS  (BEVAN).  Mental  Diseases.  A  text-book  having  special  reference  to  the 
Pathological  aspects  of  Insanity.  By  Bevan  Lewis,  l.k.c.p.,  m.r.c.s.,  Medi- 
cal Director,  West  Riding  Asylum,  Wakefield,  England.  18  Lithographic  Plates 
and  other  Illustrations.     Second  Edition.     8vo.  Cloth,  $7.00 

LINCOLN.    School  and  Industrial  Hygiene.    By  D.  F.  Lincoln,  m.d.    Cloth,  .40 
LIZARS  (JOHN).     On  Tobacco.     The  Use  and  Abuse  of  Tobacco.  Cloth,  .40 

LONGLEY'S  Pocket  Medical  Dictionary  for  Students  and  Physicians.  Giving 
the  Definition  and  Pronunciation  of  Words  and  Terms  in  General  Use  in  Medi- 
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Cloth,  .75  ;  Tucks  and  Pocket,  $1.00 

MACALISTER'S  Human  Anatomy.  800  Illustrations.  Systematic  and  Topo- 
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special  reference  to  the  requirements  of  Practical  Surgery  and  Medicine.  By 
Alex.  Macalister,  m.d.,  f.r.s.,  Professor  of  Anatomy  in  the  University  of  Cam- 
bridge, England.     816  Illustrations.     Octavo.  Cloth,  $5.00;  Leather,  $6.co 

MACDONALD'S  Microscopical  Examinations  of  Water  and  Air.  With  an  Ap- 
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25  Lithographic  Plates,  Reference  Tables,  etc.     Second  Ed.     8vo.      Cloth,  $2.50 

MACKENZIE.  The  Pharmacopoeia  of  the  London  Hospital  for  Diseases  of 
the  Throat.  By  Sir  Morell  Mackenzie,  m.d.  Fifth  Edition.  Revised  and 
Improved  by  F.  G.  Harvey,  Surgeon  to  the  Hospital.  Cloth,  $1.00 

MACREADY.  A  Treatise  on  Ruptures.  By  Jonathan  F.  C.  H.  Macready, 
f.r.c.s.,  Surgeon  to  the  Great  Northern  Central  Hospital;  to  the  City  of  London 
Hospital  for  Diseases  of  the  Chest;  to  the  City  of  London  Truss  Society,  etc. 
With  24  full-page  Plates  and  numerous  Wood-Engravings.  Octavo.     Cloth,  $6.00 

MANN.  Forensic  Medicine  and  Toxicology.  A  Text-Book  by  J.  Dixon  Mann, 
m.d.,  f.r.c.p.,  Professor  of  Medical  Jurisprudence  and  Toxicology  in  Owens  Col- 
lege, Manchester;  Examiner  in  Forensic  Medicine  in  University  of  London,  etc. 
Illustrated.     Octavo.  Cloth,  $6.50 

MANN'S  Manual  of  Psychological  Medicine  and  Allied  Nervous  Diseases.  Their 
Diagnosis,  Pathology,  Prognosis  and  Treatment,  including  their  Medico-Legal 
Aspects  ;  with  chapter  on  Expert  Testimony,  and  an  abstract  of  the  laws  relating 
to  the  Insane  in  all  the  States  of  the  Union.  By  Edward  C.  Mann,  m.d. 
With  Illustrations.     Octavo.  Cloth,  $3.00 

MARSHALL'S  Physiological  Diagrams,  Life  Size,  Colored.  Eleven  Life-size 
Diagrams  (each  7  feet  by  3  feet  7  inches).  Designed  for  Demonstration  before 
the  Class.  By  John  Marshall,  f.r.s.,  f.r.c.s.,  Professor  of  Anatomy  to  the 
Royal  Academy  ;  Professor  of  Surgery,  University  College,  London,  etc. 

In  Sheets,  $40.00     Backed  with  Muslin  and  Mounted  on  Rollers,  $60.00 
Ditto,  Spring  Rollers,  in  Handsome  Walnut  Wall  Map  Case  (Send  for 

Special  Circular), •».         .         .         .       $100.00 

Single  Plates,  Sheets,  $5.00;  Mounted,  $7.50;  Explanatory  Key,  50  cents. 
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No.  4 — The  Heart  and  Principal  Blood-vessels.  No.  5 — The  Lymphatics  or  Absorb- 
ents. No.  6 — The  Digestive  Organs.  No.  7 — The  Brain  and  Nerves.  Nos.  8  and  9 — 
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MARSHALL.  The  Woman's  Medical  College  of  Pennsylvania.  An  Historical 
Outline.    By  Clara  Marshall,  m.d.,  Dean  of  the  College.     8vo.     Cloth,  $1.50 


18  P.  BLAKISTON'S  SON  &»  CO.'S 

MASON'S  Compend  of  Electricity,  and  its  Medical  and  Surgical  Uses.  By 
Charles  F.  Mason,  m.d.,  Assistant  Surgeon  U.  S.  Army.  With  an  Intro- 
duction by  Charles  H.  May,  m.d.,  Instructor  in  the  New  York  Polyclinic. 
Numerous  Illustrations.     i2mo.  Cloth,  .75 

MAXWELL.  Terminologia  Medica  Polyglotta.  By  Dr.  Theodore  Maxwell, 
assisted  by  others  in  various  countries.     8vo.  Cloth,  $3.00 

The  object  of  this  work  is  to  assist  the  medical  men  of  any  nationality  in  reading  medical  literature  written 
in  a  language  not  their  own.  Each  term  is  usually  given  in  seven  languages,  viz.  :  English,  French,  German, 
Italian,  Spanish,  Russian  and  Latin. 

MAYLARD.  The  Surgery  of  the  Alimentary  Canal.  By  Alfred  Ernest 
Maylard,  m.b.,  B.s.,  Senior  Surgeon  to  the  Victoria  Infirmary,  Glasgow.  With 
27  Full-Page  Plates  and  117  other  Illustrations.     Octavo.  Cloth,  $7. 50 

MAYS'  Theine  in  the  Treatment  of  Neuralgia.  By  Thomas  J.  Mays,  m.d. 
i6mo.  yz  bound,  .50 

McBRIDE.  Diseases  of  the  Throat,  Nose  and  Ear.  A  Clinical  Manual  for  Stu- 
dents and  Practitioners.  By  P.  McBride,  m.d.,  f.r.c.p.  (Edin.),  Surgeon  to  the 
Ear  and  Throat  Department  of  the  Royal  Infirmary;  Lecturer  on  Diseases  of 
Throat  and  Ear,  Edinburgh  School  of  Medicine,  etc.  With  Colored  Illustrations 
from  Original  Drawings.    2d  Edition.    Octavo.       Handsome  Cloth,  Gilt  top,  $6.00 

McNEILL.  The  Prevention  of  Epidemics  and  the  Construction  and  Man- 
agement of  Isolation  Hospitals.  By  Dr.  Roger  McNeill,  Medical  Officer  ot 
Health  for  the  County  of  Argyll.  With  numerous  Plans  and  other  Illustrations. 
Octavo.  Cloth,  $3.50 

MEIGS.  Milk  Analysis  and  Infant  Feeding.  A  Treatise  on  the  Examination  of 
Human  and  Cows'  Milk,  Cream,  Condensed  Milk,  etc.,  and  Directions  as  to  the 
Diet  of  Young  Infants.     By  Arthur  V.  Meigs,  m.d.     i2mo.  Cloth,  .50 

MEMMINGER.  Diagnosis  by  the  Urine.  The  Practical  Examination  of  Urine, 
with  Special  Reference  to  Diagnosis.  By  Allard  Memminger,  m.d.,  Professor 
of  Chemistry,  Urinology,  and  Hygiene  in  the  Medical  College  of  the  State  of 
South  Carolina;  Visiting  Physician  in  the  City  Hospital  of  Charleston,  etc. 
Second  Edition,  Enlarged  and  Revised.     24  Illus.     i2mo.  Cloth,  $1.00 

MORRIS.  Text-Book  of  Anatomy.  Second  Edition.  790  Illustrations,  many 
in  Colors.  A  complete  Text-book.  Edited  by  Henry  Morris,  f.r.c.s.,  Surg, 
to,  and  Lect.  on  Anatomy  at,  Middlesex  Hospital,  assisted  by  J.  Bland  Sutton, 
f.r  c.s.,  J.  H.  Davies-Colley,  f.r.c.s.,  Wm.  J.  Walsham,  f.r.c.s.,  H.  St.  John 
Brooks,  m.d.,  R.  Marcus  Gunn,  f.r. c.s. .Arthur  Hensman, f.r. c.s., Frederick 
Treves,  f.r.c.s.,  William  Anderson,  f.r.c.s.,  and  Prof.  W.  H.  A.  Jacobson. 
One  Handsome  Octavo  Volume,  with  790  Illustrations,  of  which  many  are 
printed  in  colors.  Cloth,  $6.00;  Leather,  $7.00;  Half  Russia,  $8.00 

"Taken  as  a  whole,  we  have  no  hesitation  in  according  very  high  praise  to  this  work.  It 
will  rank,  we  believe,  with  the  leading  Anatomies.  The  illustrations  are  handsome  and  the 
printing  is  good." — Boston  Aledical  and  Surgical  Journal. 

"  The  work  as  a  whole  is  filled  with  practical  ideas,  and  the  salient  points  of  the  subject 
are  properly  emphasized.  The  surgeon  will  be  particularly  edified  by  the  section  on  the  topo- 
graphical anatomy,  which  is  full  to  repletion  of  excellent  and  useful  illustrations." — The  Medical 
Record,  Nezv  York. 

Handsome  circular,  with  sample  pages  and  colored  illustrations,  will  be  sent  free 
to  any  address. 

Renal  Surgery.  With  Special  Reference  to  Stone  in  the  Kidney  and  Ureter, 
and  to  the  Surgical  Treatment  of  Calculous  Anuria,  together  with  a  Critical 
Examination  of  Subparietal  Injuries  of  the  Ureter.     Illustrated.     8vo. 

Cloth,  $2.00 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  19 

MORTON  on  Refraction  of  the  Eye.  Its  Diagnosis  and  the  Correction  of  its  Errors. 
With  Chapter  on  Keratoscopy,  and  Test  Types.  By  A.  Morton,  m.b.  Sixth 
Edition,  Revised  and  Enlarged.  Cloth,  $1.00 

MOULLIN.  Surgery.  Third  Edition,  by  Hamilton.  A  Complete  Text-book. 
By  C.  W.  Mansell  Moullin,  m.a.,  m.d.  (Oxon.),  f.r.c.s.,  Surgeon  and  Lec- 
turer on  Physiology  to  the  London  Hospital ;  formerly  Radcliffe  Traveling 
Fellow  and  Fellow  of  Pembroke  College,  Oxford.  Third  American  Edition. 
Revised  and  edited  by  John  B.  Hamilton,  m.d.,  ll.d.,  Professor  of  the  Principles 
of  Surgery  and  Clinical  Surgery,  Rush  Medical  College,  Chicago  ;  Professor  of 
Surgery,  Chicago  Polyclinic  ;  Surgeon,  formerly  Supervising  Surgeon-General, 
U.  S.  Marine  Hospital  Service;  Surgeon  to  Presbyterian  Hospital;  Consulting 
Surgeon  to  St.  Joseph's  Hospital  and  Central  Free  Dispensary,  Chicago,  etc. 
600  Illustrations,  over  200  of  which  are  original,  and  many  of  which  are  printed 
in  Colors.     Royal  Octavo.     1250  pages. 

Handsomely  bound  in  Cloth,  $6.00;  Leather,  $7.00;  Half  Russia,  $8.00 
"  The  aim  to  make  this  valuable  treatise  practical  by  giving  special  attention  to  questions  of 
treatment  has  been  admirably  carried  out.  Many  a  reader  will  consult  the  work  with  a  feeling 
of  satisfaction  that  his  wants  have  been  understood,  and  that  they  have  been  intelligently  met. 
He  will  not  look  in  vain  for  details,  without  proper  attention  to  which  he  well  knows  that  the 
highest  success  is  impossible." — The  American  Journal  of  Medical  Sciences. 

Handsome  circular,  with  sample  pages  and  colored  illustrations,  will  be  sent  to 
any  address  upon  application. 

Enlargement  of  the   Prostate.     Its  Treatment  and   Radical   Cure.     Illus- 
trated.    Second  Edition.     Octavo.  Preparing. 
Inflammation  of  the  Bladder  and  Urinary  Fever.    Octavo.      Cloth,  $1.50 

MTJRRELL.     Massotherapeutics.     Massage  as  a  Mode  of  Treatment.     By  Wm. 
Murrell,  m.d.,  F.R.C.P.,  Lecturer  on  Pharmacology  and  Therapeutics  at  West- 
minster Hospital.     Sixth  Edition.    Revised.    i2mo.  Preparing. 
What  To  Do  in  Cases  of  Poisoning.     Seventh  Edition,  Enlarged  and  Re- 
vised.    64mo.                                                                                          Cloth,  $1.00 

MUTER.  Practical  and  Analytical  Chemistry.  By  John  Muter,  f.r.s.,  f.c.s., 
etc.  Second  American  from  the  Eighth  English  Edition.  Revised,  to  meet  the 
requirements  of  American  Medical  and  Pharmaceutical  Colleges.     56  Illus. 

Cloth,  $1.25 

NAPHEYS'  Modern  Therapeutics.  Ninth  Revised  Edition,  Enlarged  and  Im- 
proved. In  Two  Handsome  Volumes.  Edited  by  Allen  J.  Smith,  m.d.,  Pro- 
fessor of  Pathology,  University  of  Texas,  Galveston,  late  Ass't  Demonstrator  of 
Morbid  Anatomy  and  Pathological  Histology,  Lecturer  on  Urinology,  University 
of  Pennsylvania;  and  J.  Aubrey  Davis,  m.d.,  Ass't  Demonstrator  of  Obstetrics, 
University  of  Pennsylvania;  Ass't  Physician  to  Home  for  Crippled  Children,  etc. 
Vol.  I. — General  Medicine  and  Diseases  of  Children. 

Handsome  Cloth  binding,  $4.00 

Vol.  II. — General  Surgery,  Obstetrics,  and  Diseases  of  Women. 

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NEW  SYDENHAM  SOCIETY  Publications.  Three  to  Six  Volumes  published 
each  year.     List  of  Volumes  upon  application.  Per  annum,  $8.00 

NOTTER  and  FIRTH.  The  Theory  and  Practice  of  Hygiene.  A  Complete 
Treatise  by  J.  Lane  Notter,  m.a.,  m.d.,  f.c.s.,  Fellow  and  Member  of  Council 
of  the  Sanitary  Institute  of  Great  Britain  ;  Professor  of  Hygiene,  Army  Medical 
School ;  Examiner  in  Hygiene,  University  of  Cambridge,  etc.,  and  R.  H.  Firth, 
F.R.C.S.,  Assistant  Professor  of  Hygiene,  Army  Medical  School,  Netly.  Illustrated 
by  10  Lithographic  Plates  and  135  other  Illustrations,  and  including  many  Useful 
Tables.     Octavo.     1034  pages.  Cloth,  $7.00 

***This  volume  is  based  upon  Parkes'  Practical  Hygiene,  which  will  not  be  pub- 
lished hereafter. 


20  P.  BLAKISTON'S  SON  6-  CO.'S 

OETTEL.  Practical  Exercises  in  Electro-Chemistry.  By  Dr.  Felix  Oettel. 
Authorized  Translation  by  Edgar  F.  Smith,  m.a.,  Professor  of  Chemistry, 
University  of  Penns)lvania.     Illustrated.  Cloth,  .75 

Introduction  to  Electro-Chemical  Experiments.     Illustrated.     By  same 
Author  and  Translator.  Cloth,  .75 

OHLEMANN.     Ocular  Therapeutics  for  Physicians  and  Students.     By  M.  Ohle- 

manx,  m.d.,  late  Physician  in  the  Ophthalmological  Clinical  Institute,  Royal 

Prussian  University  of  Berlin,  etc.     Translated   and    Edited   by   Chakles  A. 

Oliver,   a.m.,   m.d.,  Attending   Surgeon    to  Wills  Eye  Hospital:   Ophthalmic 

Surgeon  to  the  Philadelphia  and  to  the  Presbyterian  Hospitals;  Fellow  of  the 

College  of  Physicians  of  Philadelphia,  etc.     i2mo.  Cloth,  $1.75 

*V*  No  attempt  has  been  made  for  many  years  to  treat  exhaustively  the  remedial 

agents  used  in  ophthalmology.     The  aim  of  this  book  is  to  supply  a  treatise  on  this 

subject  that  will  serve  as  a  guide  to  the  practising  physician;  and  in  no  branch  of 

therapeutics  is  the  relative  value  of  the  remedies  and  formulas  to  be  employed  so 

worthy  of  careful  consideration,  and  their  results,  when  intelligently  employed,  of  so 

much  importance  to  the  physician  and  patient. 

0RMER0D.  Diseases  of  Nervous  System,  Student's  Guide  to.  By  J.  A.  Ormerod, 
m.d.  (Oxon.),  f.r.c.p.,  Physician  to  National  Hospital  for  Paralyzed  and  Epileptic 
and  to  City  of  London  Hospital  for  Diseases  of  the  Chest,  etc.  With  66  Wood 
Engravings.     i2mo.  Cloth,  $1.00 

OSGOOD.    The  Winter  and  Its  Dangers.    By  Hamilton  Osgood,  m.d.  Cloth,  .40 

OSLER.     Cerebral  Palsies  of  Children.    A  Clinical  Study.    By  William  Osler, 

m.d.,  f.r.c.p.   (Lond.),  Professor  of  Medicine,  Johns    Hopkins  University,  etc. 

8vo.  Cloth,  $2.00 

Chorea  and  Choreiform  Affections.    8vo.  Cloth,  $2.00 

0STR0M.  Massage  and  the  Original  Swedish  Movements.  Their  Application 
to  Various  Diseases  of  the  Body.  A  Manual  for  Students,  Nurses  and  Physicians. 
By  Kurre  W.  Ostrom,  from  the  Royal  University  of  Upsala,  Sweden;  Instructor 
in  Massage  and  Swedish  Movements  in  the  Hospital  of  the  University  of 
Pennsylvania,  and  in  the  Philadelphia  Polyclinic  and  College  for  Graduates  in 
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ings, many  of  which  were  drawn  especially  for  this  purpose.    i2mo.     Cloth,  $1  00 

PACKARD'S  Sea  Air  and  Sea  Bathing.    By  John  H.  Packard,  m.d.      Cloth,  .40 

PARKES'  Practical  Hygiene.  By  Edward  A.  Parkes,  m.d.  Superseded  by 
"  Notter  and  Firth  "  Treatise  on  Hygiene.     See  previous  page. 

PARKES.  Hygiene  and  Public  Health.  A  Practical  Manual.  By  Louis  C. 
Parkes,  m.d.,  d.p.h.  Lond.  Univ.,  Lect.  on  Public  Health  at  St.  George's  Hos- 
pital, Medical  Officer  of  Health,  Parish  of  Chelsea,  London,  etc.  Fifth  Edition, 
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The    Elements    of    Health.      An    Introduction    to  the  Study   of  Hygiene. 
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PARRISH'S  Alcoholic  Inebriety.  From  a  Medical  Standpoint,  with  Illustrative 
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President  of  the  Amer.  Assoc,  for  Cure  of  Inebriates.  Cloth,  $1.00 

PHILLIPS.  Spectacles  and  Eyeglasses,  Their  Prescription  and  Adjustment.  By 
R.  J.  Phillips,  m.d.,  Instructor  on  Diseases  of  the  Eye,  Philadelphia  Polyclinic, 
Ophthalmic  Surgeon,  Presbyterian  Hospital.  Second  Edition,  Revised  and 
Enlarged.     49  Illustrations.     121110.  Cloth,  $1.00 

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the  rules  and  suggestions  contained  in  tins  little  volume  should  be  familiar  to  every  oculist  and 
optician." — The  Aledical  Record,  New   York. 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  21 

PHYSICIAN'S  VISITING  LIST.  Published  Annually.  Forty-eighth  Year  (1899) 
of  its  Publication. 

Hereafter  all  styles  will  contain  the  interleaf  or  special  memoranda  page,  except 
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.    50         "  "  2  vols,      i  t  1    *    is       r  2-°° 

(  July  to  Dec.  j 

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'  J  [  July  to  Dec.  ) 

,,  11  1         f  Tan.  to  Tune )  .,  ,,  .,         ,,         ,, 

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hence  its  popularity.    A  special  circular,  descriptive  of  contents  will  be  sent  upon 

application. 

POTTER.  A  Handbook  of  Materia  Medica,  Pharmacy,  and  Therapeutics,  in- 
cluding the  Action  of  Medicines,  Special  Therapeutics  of  Disease,  Official  and 
Practical  Pharmacy,  and  Minute  Directions  for  Prescription  Writing,  etc.  In- 
cluding over  600  Prescriptions  and  Formulae.  By  Samuel  O.  L.  Potter,  m.a., 
m.d.,  m.r.c.p.  (Lond.),  Professor  of  the  Principles  and  Practice  of  Medicine  and 
Clinical  Medicine  in  the  College  of  Physicians  and  Surgeons,  San  Francisco; 
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Compend  of  Anatomy,  including  Visceral  Anatomy.  Sixth  Edition.  Re- 
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6  t  Quiz- Compend  f  Series.    Cloth,  .80.     Interleaved  for  taking  Notes,  $1.25 

Speech  and  Its  Defects.  Considered  Physiologically,  Pathologically  and 
Remedially ;  being  the  Lea  Prize  Thesis  of  Jefferson  Medical  College,  1882. 
Revised  and  Corrected.     i2mo.  Cloth,  $1.00 

POWELL.  Diseases  of  the  Lungs  and  Pleurae,  Including  Consumption.  By 
R.  Douglas  Powell,  m.d.,  f.r.c.p.,  Physician  to  the  Middlesex  Hospital,  and 
Consulting  Physician  to  the  Hospital  for  Consumption  and  Diseases  of  the  Chest 
at  Brompton.  Fourth  Edition.  With  Colored  Plates  and  Wood  Engravings. 
8vo.  Cloth,  $4.00 

POWER.  Surgical  Diseases  of  Children  and  their  Treatment  by  Modern 
Methods.  By  DArcy  Power,  m.a.,  f.r.c.s.  (Eng.),  Demonstrator  of  Operative 
Surgery,  St.  Bartholomew's  Hospital ;  Surgeon  to  the  Victoria  Hospital  for 
Children.     Illustrated.     i2mo.  Cloth,  $2.50 


22  P.  BLAKISTON'S  SON  &•  CO.'S 

PRESTON.  Hysteria  and  Certain  Allied  Conditions.  Their  Nature  and  Treat- 
ment. With  special  reference  to  the  application  of  the  Rest  Cure,  Massage, 
Electro-therapy,  Hypnotism,  etc.  By  George  J.  Preston,  m.d.,  Professor  of 
Diseases  of  the  Nervous  System,  College  of  Physicians  and  Surgeons,  Balti- 
more ;  Visiting  Physician  to  the  City  Hospital ;  Consulting  Neurologist  to  Bay 
View  Asylum  and  the  Hebrew  Hospital ;  Member  American  Neurological  Asso- 
ciation, etc.     With  Illustrations.      i2mo.  Cloth,  $2.00 

PRITCHARD.  Handbook  of  Diseases  of  the  Ear.  By  Urban  Pritchard, 
m.d.,  f.r.c.s.,  Professor  of  Aural  Surgery,  King's  College,  London,  Aural  Sur- 
geon to  King's  College  Hospital,  Senior  Surgeon  to  the  Royal  Ear  Hospital,  etc. 
Third  Edition,  Enlarged.    Many  Illustrations  and  Formulae.    i2mo.    Cloth,  $1.50 

PROCTOR'S  Practical  Pharmacy.  Lectures  on  Practical  Pharmacy.  With  Wood 
Engravings  and  32  Lithographic  Fac -simile  Prescriptions.  By  Barnard  S. 
Proctor.  Third  Edition.  Revised  and  with  elaborate  Tables  of  Chemical 
Solubilities,  etc.  Cloth,  $3.00 

REESE'S  Medical  Jurisprudence  and  Toxicology.  A  Text-book  for  Medical  and 
Legal  Practitioners  and  Students.  By  John  J.  Reese,  m.d.,  Editor  of  Taylor's 
Jurisprudence,  Professor  of  the  Principles  and  Practice  of  Medical  Jurisprudence, 
including  Toxicology,  in  the  University  of  Pennsylvania  Medical  Department. 
Fifth  Edition.  Revised  and  Edited  by  Henry  Leffmann,  m.d.,  Pathological 
Chemist,  Jefferson  Medical  College  Hospital ;  Chemist,  State  Board  of  Health  ; 
Professor  of  Chemistry,  Woman's  Medical  College  of  Penna.,  etc.  121110.  645 
pages.  Cloth,  $3.00;   Leather,  $3.50 

"  To  the  student  of  medical  jurisprudence  and  toxicology  it  is  invaluable,  as  it  is  concise, 

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REEVES.  Medical  Microscopy.  Illustrated.  A  Handbook  for  Physicians  and 
Students,  including  Chapters  on  Bacteriology,  Neoplasms,  Urinary  Examination, 
etc.  By  James  E.  Reeves,  m.d.,  Ex-President  American  Public  Health  Associa- 
tion, Member  Association  American  Physicians,  etc.  Numerous  Illustrations, 
some  of  which  are  printed  in  colors.  i2mo.     Handsome  Cloth,  $2.50 

REGIS.  Mental  Medicine.  A  Practical  Manual.  By  Dr.  E.  Regis,  formerly 
Chief  of  Clinique  of  Mental  Diseases,  Faculty  of  Medicine  of  Paris  ;  Physician 
of  the  Maison  de  Sante  de  Castel  d'Andorte  ;  Professor  of  Mental  Diseases, 
Faculty  of  Medicine,  Bordeaux,  etc.  With  a  Preface  by  M.  Benjamin  Ball, 
Clinical  Professor  of  Mental  Diseases,  Faculty  of  Medicine,  Paris.  Authorized 
Translation  from  the  Second  Edition  by  H.  M.  Bannister,  m.d.,  late  Senior 
Assistant  Physician,  Illinois  Eastern  Hospital  for  the  Insane,  etc.  With  an  In- 
troduction by  the  Author.     i2mo.     692  pages.  Cloth,  $2.00 

RICHARDSON.  Long  Life,  and  How  to  Reach  It.  By  J.  G.  Richardson,  Prof, 
of  Hygiene,  University  of  Pennsylvania.  Cloth,  .40 

RICHARDSON'S  Mechanical  Dentistry.  A  Practical  Treatise  on  Mechanical 
Dentistry.  By  Joseph  Richardson,  d.d.s.  Seventh  Edition.  Thoroughly 
Revised  and  in  many  parts  Rewritten  by  Dr.  Geo.  W.  Warren,  Chief  of  the 
Clinical  Staff,  Pennsylvania  College  of  Dental  Surgery,  Philadelphia.  With  691 
Illustrations,  many  of  which  are  from  original  Wood  Engravings.  Octavo. 
675  pages.  Cloth,  $5.00;  Leather,  $6.00 ;  Half  Russia,  $7.00 

ROBERTS.  Practice  of  Medicine.  The  Theory  and  Practice  of  Medicine.  By 
Frederick  Roberts,  m.d.,  Professor  of  Therapeutics  at  University  College, 
London.    Ninth  Edition,  with  Illustrations.    8vo.        Cloth,  $4.50;  Leather,  $5.50 

ROBERTS.  Fractures  of  the  Radius.  A  Clinical,  Pathological,  and  Experimental 
Study.  By  John  B.  Roberts,  m.d.,  Professor  of  Anatomy  and  Surgery  in  the 
Philadelphia  Polyclinic,  etc.     33  Illustrations.     8vo.  Cloth,  $1.00 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS^ 23 

RICHTERS  Inorganic  Chemistry.    A  Text-book  for  Students.    By  Prof.  Victor 

von   Richter,    University  of  Breslau.     Fourth  American,  from  Sixth  German 

Edition.      Authorized   Translation   by  Edgar  F.  Smith,  m.a.,  ph.d.,  Prof,  of 

Chemistry,  University  of  Pennsylvania,  Member  of  the  Chemical  Societies  of 

Berlin  and  Paris.    89  Illustrations  and  a  Colored  Plate,     iamo.  Cloth,  $1.75 

Organic  Chemistry.      The  Chemistry  of  the   Carbon    Compounds.      Third 

American  Edition,  translated  from  the  Eighth  German  by  Edgar  F.  Smith, 

m.a.,  PH.D.,  Professor  of  Chemistry,  University  of  Pennsylvania.  Revised  and 

Enlarged.     Illus.     2  vols.     i2mo.     Vol.  I.     Aliphatic  Series.     625  pages. 

Cloth,  $3.00 
Vol.  II.     Aromatic  Series.     Preparing. 

ROBINSON.  Latin  Grammar  of  Pharmacy  and  Medicine.  By  D.  H.  Robinson, 
ph.d.,  Professor  of  Latin  Language  and  Literature,  University  of  Kansas.  Intro- 
duction by  L.  E.  Sayre,  ph.g.,  Professor  of  Pharmacy  in,  and  Dean  of  the  Dept. 
of  Pharmacy,  University  of  Kansas.  Third  Edition.  Revised  with  the  help 
of  Prof.  L.  E.  Sayre,  of  University  of  Kansas,  and  Dr.  Charles  Rice,  of  the 
College  of  Pharmacy  of  the  City  of  New  York.     i2mo.  Cloth,  $1.75 

ST,  CLAIR.  Medical  Latin.  Designed  expressly  for  the  Elementary  Training 
of  Medical  Students.  By  W.  T.  St.  Clair,  Instructor  in  Latin  in  the  Kentucky 
School  of  Medicine  and  in  the  Louisville  Male  High  School.    i2mo.    Cloth,  $1.00 

SANSOM.  Diseases  of  The  Heart.  The  Diagnosis  and  Pathology  of  Diseases  of 
the  Heart  and  Thoracic  Aorta.  By  A.  Ernest  Sansom,  m.d.,  f.r.c.p.,  Physician 
to  the  London  Hospital,  etc.     With  Illustrations.     8vo.  Cloth,  $6.00 

SAYRE.  Organic  Materia  Medica  and  Pharmacognosy.  An  Introduction 
to  the  Study  of  the  Vegetable  Kingdom  and  the  Vegetable  and  Animal  Drugs. 
Comprising  the  Botanical  and  Physical  Characteristics,  Source,  Constituents,  and 
Pharmacopceial  Preparations.  With  Chapters  on  Synthetic  Organic  Remedies, 
Insects  Injurious  to  Drugs,  and  Pharmacal  Botany.  By  L.  E.  Sayre,  ph.g., 
Professor  of  Pharmacy  and  Materia  Medica  in  the  University  of  Kansas,  Mem- 
ber of  the  Committee  of  Revision  of  the  U.  S.  Pharmacopoeia,  1890.  A  Glossary 
and  543  Illustrations.     Second  Edition.  Preparing. 

SCHAMBERGr.  Compend  of  Diseases  of  the  Skin.  By  Jay  F.  Schamberg, 
Associate  in  Skin  Diseases,  Philadelphia  Polyclinic ;  Quiz-Master  at  University 
of  Pennsylvania.     99  Illustrations.  Cloth,  .80.     Interleaved,  $1.25 

SCHREINER.  Diet  List.  Arranged  in  the  Form  of  a  Chart  on  which  Articles  of 
Diet  can  be  indicated  for  any  Disease.  By  E.  R.  Schreiner,  m.d.,  Ass't  Dem. 
of  Physiology,  University  of  Penna.  Put  up  in  Pads  of  50  with  Pamphlet  of 
Specimen  Dietaries.  Per  Pad,    .75 

SCHULTZE.  Obstetrical  Diagrams.  Being  a  Series  of  20  Colored  Lithograph 
Charts,  imperial  map  size,  of  Pregnancy  and  Midwifery,  with  accompanying 
explanatory  (German)  text,  illustrated  by  wood-cuts.  By  Dr.  B.  S.  Schultze, 
Professor  of  Obstetrics,  University  of  Jena.     Second  Revised  Edition. 

Price,  in  Sheets,  $26.00 ;  Mounted  on  Rollers,  Muslin  Backs,  $36.00 

SCOVILLE.  The  Art  of  Compounding.  A  Text-book  for  Students  and  a  Refer- 
ence Book  for  Pharmacists.  By  Wilbur  L.  Scoville,  ph.g.,  Professor  of  Ap- 
plied Pharmacy  and  Director  of  the  Pharmaceutical  Laboratory  in  the  Massa- 
chusetts College  of  Pharmacy.     Second  Edition,  Enlarged  and  Improved. 

Cloth,  $2.50;  Sheep,  $3.50;  Half  Russia,  $4.50 

SEWELL.  Dental  Surgery,  including  Special  Anatomy  and  Surgery.  By  Henry 
Sewell,  m.r.c.s.,  l.d.s.,  President  Odontological  Society  of  Great  Britain.  3d 
Edition,  greatly  enlarged,  with  about  200  Illustrations.  Cloth,  $2.00 

SHAWE.  Notes  for  Visiting  Nurses,  and  all  those  interested  in  the  working  and 
organization  of  District,  Visiting,  or  Parochial  Nurse  Societies.  By  Rosalind 
Gillette  Shawe,  District  Nurse  for  the  Brooklyn  Red  Cross  Society.  With  an 
Appendix  explaining  the  organization  and  working  of  various  Visiting  and  Dis- 
trict Nurse  Societies,  by  Helen  C.  Jenks,  of  Philadelphia.     i2mo.    Cloth,  $1.00 


24  P.  BLAKISTON'S  SON  &*  CO.'S 

SMITH.  Abdominal  Surgery.  Being  a  Systematic  Description  of  all  the  Princi- 
pal Operations.  By  J.  Greig  Smith,  m.a.,  f.r.s.e.,  Surg,  to  British  Royal  In- 
firmary. 224  Illustrations.  Sixth  Edition.  Enlarged  and  Thoroughly  Revised 
by  James  Swain,  m.d.  (Lond.),  f.r.c.s.,  Professor  of  Surgery,  University  College, 
Bristol,  etc.     2  Volumes.     Octavo.  Cloth,  $10.00 

SMITH.  Electro-Chemical  Analysis.  By  Edgar  F.  Smith,  Professor  of  Chem- 
istry, University  of  Pennsylvania.  Second  Edition,  Revised  and  Enlarged.  27 
Illustrations.     121110.  Cloth,  $1.25 

***  See  also  Oettel  and  Richter. 

SMITH  and  KELLER.  Experiments.  Arranged  for  Students  in  General  Chem- 
istry. By  Edgar  F.  Smith,  Professor  of  Chemistry,  University  of  Pennsylvania, 
and  Dr.  H.  F.  Keller,  Professor  of  Chemistry,  Philadelphia  High  School.  Third 
Edition.     8vo.     Illustrated.  Cloth,  .60 

SMITH.  Dental  Metallurgy.  A  Manual.  By  Ernest  A.  Smith,  f.c.s.,  Asst. 
Instructor  in  Metallurgy  Royal  College  of  Science,  London.     Illustrated.     i2mo. 

Cloth,  $1.75 

STAMMER.  Chemical  Problems,  with  Explanations  and  Answers.  By  Karl 
Stammer.  Translated  from  the  Second  German  Edition,  by  Prof.  W.  S.  Hos- 
kinson,  a.m.,  Wittenberg  College,  Springfield,  Ohio.     i2mo.  Cloth.  .50 

STARLING.  Elements  of  Human  Physiology.  By  Ernest  H.  Starling,  m.d. 
Lond.,  m.r.c.p.,  Joint  Lecturer  on  Physiology  at  Guy's  Hospital,  London, 
etc.     With  100  Illustrations.      121110.     437  pages.  Cloth,  $1.00 

STARR.  The  Digestive  Organs  in  Childhood.  Second  Edition.  The  Diseases 
of  the  Digestive  Organs  in  Infancy  and  Childhood.  With  Chapters  on  the 
Investigation  of  Disease  and  the  Management  of  Children.  By  Louis  Starr, 
m.d..  late  Clinical  Prof,  of  Diseases  of  Children  in  the  Hospital  of  the  University 
of  Penn'a;  Physician  to  the  Children's  Hospital,  Phila.  Second  Edition. 
Revised  and  Enlarged.  Illustrated  by  two  Colored  Lithograph  Plates  and 
numerous  Wood  Engravings.     Crown  Octavo.  Cloth,  $2.00 

The  Hygiene  of  the  Nursery,  including  the  General  Regimen  and  Feed- 
ing of  Infants  and  Children,  and  the  Domestic  Management  of  the  Ordinary 
Emergencies  of  Early  Life,  Massage,  etc.  Sixth  Edition.  Enlarged.  25 
Illustrations.     121110.     280  pages.  Cioth,  $1.00 

STEARNS.  Lectures  on  Mental  Diseases.  By  Henry  Putnam  Stearns,  m.d., 
Physician  Superintendent  at  the  Hartford  Retreat,  Lecturer  on  Mental  Diseases 
in  Yale  University,  Member  of  the  American  Medico-Psychological  Ass'n,  Hon- 
orary Member  of  the  British  Medico  Pyschological  Society.  With  a  Digest  of 
Laws  of  the  Various  States  Relating  to  Care  of  Insane.    Illustrated. 

Cloth,  $2.75  ;  Sheep,  $3.25 
STEVENSON  and  MURPHY.    A  Treatise  on  Hygiene.    By  Various  Authors. 
Edited  by  Thomas  Stevenson,  m.d.,  f  r.c.p.,  Lecturer  on  Chemistry  and  Medi- 
cal Jurisprudence  at  Guy's    Hospital,  London,  etc.,  and  Shirley  F.  Murphy, 
Medical  Officer  of  Health  to  the  County  of  London.    In  Three  Octavo  Volumes. 
Vol.  I.    With  Plates  and  Wood  Engravings.   Octavo.  Cloth,  $6.00 

Vol.11.     With  Plates  and  Wood  Engravings.     Octavo.  Cloth,  £6.00 

Vol.  III.     Sanitary  Law.     Octavo.  Cloth,  $5.00 

***  Special  Circular  upon  application. 

STEWART'S  Compend  of  Pharmacy.  Based  upon  "  Remington's  Text-Book  of 
Pharmacy."  By  F.  E.  Stewart,  m.d.,  ph. g., Quiz-Master  in  Chem.  and  Theoreti- 
cal Pharmacy,  Phila.  College  of  Pharmacy ;  Lect.  in  Pharmacology,  Jefferson 
Medical  College.  Fifth  Ed.  Revised  in  accordance  with  U.  S.  P.,  1890.  Com- 
plete tables  of  Metric  and  English  Weights  and  Measures.  ? Quiz-  Compend ? 
Series.  Cloth,  .80;  Interleaved  for  the  addition  of  notes, $1.25 

STIRLING.  Outlines  of  Practical  Physiology.  Including  Chemical  and  Experi- 
mental Physiology,  with  Special  Reference  to  Practical  Medicine.  By  W.  Stir- 
ling, m.d.,  Sc.d.,  Professor  of  Physiology  and  Histology,  Owens  College,  Victoria 
University,  Manchester.  Examiner  in  Physiology,  Universities  of  Edinburgh 
and  London.     Third  Edition.     289  Illustrations.  Cloth,  $2.00 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  25 

STIRLING.  Outlines  of  Practical  Histology.  368  Illustrations.  Second  Edi- 
tion.    Revised  and  Enlarged,  with  new  Illustrations.     i2mo.  Cloth,  $2.00 

STOHR.      Text-Book  of  Histology,  Including    the   Microscopical    Technic. 

By  Dr.  Philipp  Stohr,  Professor  of  Anatomy  at  University  of  Wiirzburg. 
Authorized  Translation  by  Emma  L.  Billstein,  m.d.,  Demonstrator  of  Histology 
and  Embryology,  Woman's  Medical  College  of  Pennsylvania.  Edited,  with 
Additions,  by  Dr.  Alfred  Schaper,  Demonstrator  of  Histology  and  Embry- 
ology, Harvard  Medical  School,  Boston.  Second  American  from  the  Eighth 
German  Edition,  Enlarged  and  Revised.    292  Illustrations.    Octavo.    Cloth,  $3.00 

STRAHAN.  Extra-Uterine  Pregnancy.  The  Diagnosis  and  Treatment  of  Extra- 
Uterine  Pregnancy.  Being  the  Jenks  Prize  Essay  of  the  College  of  Physicians 
of  Philadelphia.  By  John  Strahan,  m.d.  (Univ.  of  Ireland),  late  Res.  Surgeon 
Belfast  Union  Infirmary  and  Fever  Hospital.     Octavo.  Cloth,  .75 

SUTTON'S  Volumetric  Analysis.  A  Systematic  Handbook  for  the  Quantitative 
Estimation  of  Chemical  Substances  by  Measure,  Applied  to  Liquids,  Solids  and 
Gases.  Adapted  to  the  Requirements  of  Pure  Chemical  Research,  Pathological 
Chemistry,  Pharmacy,  Metallurgy,  Photography,  etc.,  and  for  the  Valuation  of 
Substances  Used  in  Commerce,  Agriculture,  and  the  Arts.  By  Francis  Sutton, 
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Cloth,  $4.50 

SWAIN.  Surgical  Emergencies,  together  with  the  Emergencies  Attendant  on 
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Practitioner,  and  Head  Nurse.  By  William  Paul  Swain,  f.r.c.s.,  Surgeon  to 
the  South  Devon  and  East  Cornwall  Hospital,  England.  Fifth  Edition.  i2mo. 
149  Illustrations.  Cloth,  $1.75 

SWANZY.    Diseases  of  the  Eye  and  their  Treatment.    A  Handbook  for  Physi- 
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the  National  Eye  and  Ear  Infirmary  ;  Ophthalmic  Surgeon  to  the  Adelaide  Hos- 
pital, Dublin.     Sixth    Edition,  Thoroughly  Revised  and  Enlarged.     158  Illus- 
trations, one  Plain  Plate,  and  a  Zephyr  Test  Card.     i2mo.  Cloth,  $3.00 
"  Is  without  doubt  the  most  satisfactory  manual  we  have  upon  diseases  of  the  eye.     It  occu- 
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encyclopedic  treatises,  which  are  too  extended  and  detailed  to  be  of  special  use  to  the  general 
practitioner." — Chicago  Medical  Recorder. 

SYMONDS.  Manual  of  Chemistry,  for  Medical  Students.  By  Brandreth 
Symonds,  a.m.,  m.d.,  Ass't  Physician  Roosevelt  Hospital,  Out- Patient  Department ; 
Attending  Physician  Northwestern  Dispensary,  New  York.  Second  Edition.' 
i2mo.  Cloth,  $2.00 

TAFT.  Index  of  Dental  Periodical  Literature.  By  Jonathan  Taft,  d.d.s. 
8vo.  Cloth,  $2.00 

TALBOT.  Irregularities  of  the  Teeth,  and  Their  Treatment.  By  Eugene  S. 
Talbot,  m.d.,  Professor  of  Dental  Surgery  Woman's  Medical  College,  and 
Lecturer  on  Dental  Pathology  in  Rush  Medical  College,  Chicago.  Second  Edi- 
tion, Revised.     Octavo.      234  Illustrations.     261  pages.  Cloth,  $3.00 

TANNER'S  Memoranda  of  Poisons  and  their  Antidotes  and  Tests.  By  Thos. 
Hawkes  Tanner,  m.d.,  f.r.c.p.  7th  American,  from  the  Last  London  Edition. 
Revised  by  John  J.  Reese,  m.d.,  Professor  Medical  Jurisprudence  and  Toxi- 
cology in  the  University  of  Pennsylvania.     i2mo.  Cloth,  .75 

TAYLOR.  Practice  of  Medicine.  A  Manual.  By  Frederick  Taylor,  m.d., 
Physician  to,  and  Lecturer  on  Medicine  at,  Guy's  Hospital,  London  ;  Physician  to 
Evelina  Hospital  for  Sick  Children,  and  Examiner  in  Materia  Medica  and  Phar- 
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20  P.  BLAKISTON'S  SON  6-  CO.'S 


TAYLOR  AND  WELLS.  Diseases  of  Children.  A  Manual  for  Students  and 
Physicians.  By  John  Madison  Taylor,  a.b.,  m.d.,  Professor  of  Diseases  of 
Children,  Philadelphia  Polyclinic ;  Assistant  Physician  to  the  Children's  Hospi- 
tal and  to  the  Orthopedic  Hospital;  Consulting  Physician  to  the  Elwyn  and  the 
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Howard  Hospital,  etc. ;  and  William  H.  Wells,  m.d.,  Adjunct-Professor  of 
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cal College.    With  8  Plates  and  numerous  other  Illustrations.    i2mo.    743  pages. 

Cloth,  $4.00 

Synopsis  of  Contents. — Physiology  of  the  Infant  and  Child — Diseases  Occur- 
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THOMPSON.  Urinary  Organs.  Diseases  of  the  Urinary  Organs.  Containing  32 
Lectures.  By  Sir  Henry  Thompson,  f.r.c.S.,  Emeritus  Professor  of  Clinical  Sur- 
gery in  University  College.  Eighth  London  Edition.  121  Illustrations.  Octavo. 
470  pages.  Cloth,  $3.00 

THORINGrTON.  Retinoscopy  (The  Shadow  Test)  in  the  Determination  of 
Refraction  at  One  Metre  Distance  with  the  Plane  Mirror.  By  J[ames  Thoring- 
ton,  m.d.,  Adjunct  Professor  of  Diseases  of  the  Eye  in  the  Philadelphia  Poly- 
clinic ;  Ophthalmologist  to  the  Vineland  Training  School  and  to  the  M.  E. 
Orphanage ;  Lecturer  on  the  Anatomy,  Physiology,  and  Care  of  the  Eyes  in  the 
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which  are  Colored.     Third  Edition,  Enlarged.     i2mo.  Cloth,  $1.00 

TOMES'  Dental  Anatomy.    A  Manual  of  Dental  Anatomy,  Human  and  Compara- 
tive.    By  C.  S.  Tomes,  d.d.s.     263  Illustrations.     5th  Ed.     i2mo.      Cloth,  $4.00 
Dental  Surgery.     A  System  of   Dental  Surgery.    By  John  Tomes,  f.r.s. 
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TRAUBE.  Physico-Chemical  Methods.  By  Dr.  J.  Traube,  Privatdocent  in 
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din, Harrison  Senior  Fellow  in  Chemistry,  University  of  Pennsylvania.  With 
97  Illustrations.     8vo.  Cloth,  $1.50 

TREVES.  German-English  Medical  Dictionary.    By  Frederick  Treves,  f.r.c.s., 

assisted  by  Dr.  Hugo  Lang,  b.a.  (Munich).     i2mo.  }i  Russia,  $3.25 

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TUKE.  Dictionary  of  Psychological  Medicine.  Giving  the  Definition,  Ety- 
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MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  27 

TURNBULL'S  Artificial  Anaesthesia.  A  Manual  of  Anesthetic  Agents  in  the 
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vised and  Enlarged.     54  Illustrations.     i2mo.  Cloth,  $2.50 

TUSON.  Veterinary  Pharmacopoeia,  including  the  outlines  of  Materia  Medica 
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inary College.  Fifth  Edition.  Revised  and  Edited  by  James  Bayne,  f.c.s., 
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TYSON.    The  Practice  of  Medicine.    A  Text-Book  for  Physicians  and  Students, 
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28  P-  BLAKISTON'S  SON  &*  CO.'S 

VAN  HARLINGEN  on  Skin  Diseases.  A  Practical  Manual  of  Diagnosis  and 
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Harlingen,  m.d.,  Professor  of  Diseases  of  the  Skin  in  the  Philadelphia  Poly- 
clinic ;  Clinical  Lecturer  on  Dermatology  at  Jefferson  Medical  College.  Third 
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VAN  NTJYS  on  The  Urine.  Chemical  Analysis  of  Healthy  and  Diseased  Urine, 
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Indiana  University.     39  Illustrations.     Octavo.  Cloth,  $1.00 

VIRCHOW'S  Post-mortem  Examinations.  A  Description  and  Explanation  of  the 
Method  of  Performing  them  in  the  Dead-House  of  the  Berlin  Charite  Hospital, 
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lated by  Dr.  T.  P.  Smith.    Illustrated.    Third  Edition,  with  Additions.    Cloth,  .75 

VOSWINKEL.  Surgical  Nursing.  A  Manual  for  Nurses.  By  Bertha  M.  Vos- 
winkel,  Graduate  Episcopal  Hospital,  Philadelphia;  Nurse  in  Charge  Children's 
Hospital,  Columbus,  O.  Second  Edition,  Revised  and  Enlarged,  m  Illus- 
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WALKER.  Students'  Aid  in  Ophthalmology.  By  Gertrude  A.  Walker, 
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WALSHAM.  Surgery  ;  its  Theory  and  Practice.  For  Students  and  Physicians. 
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London.    Sixth  Edition,  Revised  and  Enlarged.  With  410  Engravings.  Clo.,  $3.00 

WARD.  Notes  on  Massage;  Including  Elementary  Anatomy  and  Physiology. 
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WARING.  Practical  Therapeutics.  A  Manual  for  Physicians  and  Students.  By 
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WARREN.  Compend  Dental  Pathology  and  Dental  Medicine.  Containing  all 
the  most  noteworthy  points  of  interest  to  the  Dental  Student  and  a  Chapter 
on  Emergencies.  By  Geo.  W.  Warren,  d.d.s.,  Clinical  Chief,  Penn'a  College 
of  Dental  Surgery,  Phila.  Third  Edition,  Enlarged.  Illustrated.  Being  No. 
1  j  f  Quiz-Cotnpendf  Series.     i2mo.  Cloth,  .80 

Interleaved  for  the  addition  of  Notes,  $1.25 

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WATSON  on  Amputations  of  the  Extremities  and  Their  Complications.  By 
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Concussions.     An  Experimental  Study  of  Lesions  arising  from  Severe  Con- 
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Physicians  of  Philadelphia.  150  Illustrations,  t Quiz- Com pettdt  Series  No.y. 
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WETHERED.  Medical  Microscopy.  A  Guide  to  the  Use  of  the  Microscope  in 
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Practical  Medicine,  Middlesex  Hospital  Medical  School ;  Assistant  Physician, 
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Colored  Plate  and  101  Illustrations.     406  Pages.     i2mo.  Cloth,  $2.00 


MEDICAL  AND  SCIENTIFIC  PUBLICATION^ 29 

WEYL.  Sanitary  Relations  of  the  Coal-Tar  Colors.  By  Theodore  Weyl. 
Authorized  Translation  by  Henry  Leffmann,  m.d.,  ph.d.     i2mo.     154  pages. 

Cloth,  $1.25 

WHITACRE.  Laboratory  Text-Book  of  Pathology.  By  Horace  J.  Whitacre, 
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trated with  121  original  Illustrations.     8vo.  Cloth,  $1-5° 

WHITE.    The  Mouth  and  Teeth.    By  J.  W.  White,  m.d.,  d.d.s.  Cloth,  .40 

WHITE  AND  WILCOX.  Materia  Medica,  Pharmacy,  Pharmacology,  and 
Therapeutics.  A  Handbook  for  Students.  By  W.  Hale  White,  m.d.,  f.r.c.p., 
etc.,  Physician  to  and  Lecturer  on  Materia  Medica  and  Therapeutics,  Guy's  Hos- 
pital; Examiner  in  Materia  Medica  to  the  Conjoint  Board,  etc.  Fourth  American 
Edition.  Revised  by  Reynold  W.  Wilcox,  m.a.,  m.d.,  ll.d.,  Professor  of  Clin- 
ical Medicine  and  Therapeutics  at  the  New  York  Post- Graduate  Medical  School 
and  Hospital ;  Visiting  Physician  St.  Mark's  Hospital ;  Assistant  Visiting  Physi- 
cian Bellevue  Hospital.    Fourth  Edition,  thoroughly  Revised.    i2mo.    704  pages. 

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WILLIAMS.  Manual  of  Bacteriology.  By  Herbert  U.  Williams,  m.d.,  Pro- 
fessor of  Pathology  and  Bacteriology,  Medical  Department  University  of  Buffalo. 
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WILSON.  Handbook  of  Hygiene  and  Sanitary  Science.  By  George  Wilson, 
m.a.,  m.d.,  f.r.s.e.,  Medical  Officer  of  Health  for  Mid- Warwickshire,  England. 
With  Illustrations.     Eighth  Edition.    i2mo.  Cloth,  $3.00 

WILSON.  The  Summer  and  its  Diseases.  By  James  C.  Wilson,  m.d.,  Prof,  of  the 
Practice  of  Med.  and  Clinical  Medicine,  Jefferson  Med.  Coll.,  Phila.     Cloth,  .40 

WILSON.  System  of  Human  Anatomy,  nth  Revised  Edition.  Edited  by  Henry 
Edward  Clark,  m.d.,  m.r.c.s.  492  Illustrations,  26  Colored  Plates,  and  a 
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WINCKEL.  Text-Book  of  Obstetrics  ;  Including  the  Pathology  and  Therapeutics 
of  the  Puerperal  State.  By  Dr.  F.  Winckel,  Professor  of  Gynecology  and 
Director  of  the  Royal  University  Clinic  for  Women  in  Munich.  Authorized 
Translation  by  J.  Clifton  Edgar,  a.m.,  m.d.,  Adjunct  Professor  to  the  Chair  of 
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Handsome  Illustrations,  the  majority  of  which  are  original  with  this  work.  Octavo. 

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Revised  by  T.  Manners  Smith,  m.r.c.s.,  with  Colored  and  other  Illustrations. 
i2mo.  Cloth,  $1.00 

WOAKES.  Deafness,  Giddiness,  and  Noises  in  the  Head.  By  Edward 
Woakes,  m.d.,  Senior  Aural  Surgeon,  London  Hospital;  assisted  by  Claud 
Woak.es,  m.r.c.s.,  Assistant  Surgeon  to  the  London  Throat  Hospital.  Fourth 
Edition.     Illustrated.     i2mo.  Cloth,  $2.00 

WOOD.  Brain  Work  and  Overwork.  By  Prof.  H.  C.  Wood,  Clinical  Professor 
of  Nervous  Diseases,  University  of  Pennsylvania.     i2mo.  Cloth,  .40 

WOODY.  Essentials  of  Chemistry  and  Urinalysis.  By  Sam  E.  Woody,  a.m., 
m.d.,  Professor  of  Chemistry  and  Public  Hygiene,  and  Clinical  Lecturer  on 
Diseases  of  Children,  in  the  Kentucky  School  of  Medicine.  Fourth  Edition. 
Illustrated.     i2mo.  In  Press. 

YEO.  Manual  of  Physiology.  Third  Edition.  A  Text-book  for  Students  of 
Medicine.  By  Gerald  F.  Yeo.,  m.d.,  f.r.c.s.,  Professor  of  Physiology  in  King's 
College,  London.  Third  Edition ;  revised  and  enlarged  by  the  author.  With 
254  Wood  Engravings  and  a  Glossary.     Crown  Octavo.  Cloth,  $2.50 


From  the  Southern  Clinic. 

"  We  know  of  no  series  of  books  issued  by  any  house  that  so  fully  meets  our  approval  as  these 
?  Quiz-Compends  ?.  They  are  well  arranged,  full,  and  concise,  and  are  really  the  best  line  of  text- 
books that  could  be  found  for  either  student  or  practitioner." 


BLAKISTON'S  ? QUIZ-COMPENDS? 

The  Best  Series  of  Manuals  for  the  Use  of  Students. 

Price  of  each,  Cloth,  .80.         Interleaved  for  taking  Notes,  $1.25. 

ggp"*  These  Compends  are  based  on  the  most  popular  text-books  and  the  lectures  of  promi- 
nent professors,  and  are  kept  constantly  revised,  so  that  they  may  thoroughly  represent  the 
present  state  of  the  subjects  upon  which  they  treat.  The  authors  have  had  large  experience  as 
Quiz-Masters  and  attaches  of  colleges,  and  are  well  acquainted  with  the  wants  of  students.  They 
are  arranged  in  the  most  approved  form,  thorough  and  concise,  containing  over  600  fine  illustra- 
tions, inserted  wherever  they  could  be  used  to  advantage.  Can  be  used  by  students  of  any 
college,  and  contain  information  nowhere  else  collected  in  such  a  condensed,  practical  shape. 

ILLUSTRATED  CIRCULAR  FREE. 

No.  1.  HUMAN  ANATOMY.  Sixth  Revised  and  Enlarged  Edition.  Including  Vis- 
ceral Anatomy.  Can  be  used  with  either  Morris's  or  Gray's  Anatomy.  117  Illustrations 
and  16  Lithographic  Plates  of  Nerves  and  Arteries,  with  Explanatory  Tables,  etc.  By 
Samuel  O.  L.  Potter,  m.d.  ,  Professor  of  the  Practice  of  Medicine,  College  of  Physicians 
and  Surgeons,  San  Francisco;  late  A.  A.  Surgeon,  U.  S.  Army. 

No.  2.  PRACTICE  OF  MEDICINE.  Parti.  Sixth  Edition,  Revised,  Enlarged,  and 
Improved.  By  Dan'l  E.  Hughes,  m.d.,  Physician-in  Chief,  Philadelphia  Hospital,  late 
Demonstrator  of  Clinical  Medicine,  Jefferson  Medical  College,  Philadelphia. 

No.  3.  PRACTICE  OF  MEDICINE.  Part  II.  Sixth  Edition,  Revised,  Enlarged,  and 
Improved.     Same  author  as  No.  2. 

No.  4.  PHYSIOLOGY.  Ninth  Edition,  with  new  Illustrations  and  a  table  of  Physio- 
logical Constants.  Enlarged  and  Revised.  By  A.  P.  Brubaker,  m.d.,  Professor  of 
Physiology  and  General  Pathology  in  the  Pennsylvania  College  of  Dental  Surgery;  Demon- 
strator of  Physiology,  Jefferson  Medical  College,  Philadelphia. 

No.  5.  OBSTETRICS.  Sixth  Edition.  By  Henry  G.  Landis,  m.d.  Revised  and  Edited 
by  Wm.  H.  Wells,  m.d.,  Instructor  of  Obstetrics,  Jefferson  Medical  College,  Philadelphia. 
Enlarged.     3  Plates  and  47  other  Illustrations. 

No.  6.  MATERIA  MEDICA,  THERAPEUTICS,  AND  PRESCRIPTION 
WRITING.  Sixth  Revised  Edition  (U.  S.  P.  1890).  By  Samuel  O.  L.  Potter,  m.d., 
Professor  of  the  Practice  of  Medicine,  College  of  Physicians  and  Surgeons,  San  Francisco. 

No.  7.  GYNECOLOGY.  By  Wm.  H.  Wells,  m.d.,  Instructor  of  Obstetrics,  Jefferson 
Medical  College,  Philadelphia.      150  Illustrations. 

No.  8.  DISEASES  OF  THE  EYE  AND  REFRACTION.  A  New  Book.  Includ- 
ing Treatment  and  Surgery  and  a  Section  on  Local  Therapeutics.  By  George  M.  Gould, 
m.d.,  and  W.  L.  Pyle,  m.d.  With  Formulae,  Glossary,  several  useful  Tables,  and  in 
Illustrations,  several  of  which  are  colored. 

No.  9.  SURGERY,  Minor  Surgery,  and  Bandaging.  Fifth  Edition,  Enlarged  and  Im- 
proved. By  Orville  Horwitz,  b.s.,  m.d.,  Clinical  Professor  of  Genito-Urinary  Surgery 
and  Venereal  Diseases  in  Jefferson  Medical  College ;  Surgeon  to  Philadelphia  Hospital,  etc. 
With  98  Formulae  and  167  Illustrations. 

No.  10.  MEDICAL  CHEMISTRY.  Fourth  Edition.  Including  Urinalysis,  Animal 
Chemistry,  Chemistry  of  Milk,  Blood,  Tissues,  the  Secretions,  etc.  By  Henry  Leffmann, 
m.d.,  Professor  of  Chemistry  in  Pennsylvania  College  of  Dental  Surgery  and  in  the 
Woman's  Medical  College,  Philadelphia. 

No.  n.  PHARMACY.  Fifth  Edition.  Based  upon  Prof.  Remington's  Text-Book  of  Phar- 
macy. By  F.  E.  Stewart,  m.d.,  ph.g.,  late  Quiz-Master  in  Pharmacy  and  Chemistry, 
Philadelphia  College  of  Pharmacy ;   Lecturer  at  Jefferson  Medical  College. 

No.  12.  VETERINARY  ANATOMY  AND  PHYSIOLOGY.  Illustrated.  By 
Wm.  R.  Ballou,  m.d.,  Professor  of  Equine  Anatomy  at  New  York  College  of  Veterinary 
Surgeons;    Physician  to  Bellevue  Dispensary,  etc.     With  29  graphic  Illustrations. 

No.  13.  DENTAL  PATHOLOGY  AND  DENTAL  MEDICINE.  Third  Edition, 
Illustrated.  Containing  all  the  most  noteworthy  points  of  interest  to  the  Dental  Student  and 
a  Section  on  Emergencies.  By  Geo.  W.  Warren,  d.d.s.,  Chief  of  Clinical  Staff,  Pennsyl- 
vania College  of  Dental  Surgery,  Philadelphia. 

No.  14.  DISEASES  OF  CHILDREN.  Colored  Plate.  By  Marcus  P.  Hatfield, 
Professor  of  Diseases  of  Children,  Chicago  Medical  College.      Second  Edition,  Enlarged. 

No.  15.  GENERAL  PATHOLOGY  AND  MORBID  ANATOMY.  91  Illustra- 
tions. By  H.  Newberry  Hall,  ph.g.,  m.d.,  Professor  of  Pathology  and  Medical  Chem- 
istry, Chicago  Post-Graduate  Medical  School.     Second  Edition. 

No.  16.  DISEASES  OF  THE  SKIN.  By  Jay  F.  Schamberg,  m.d.,  Instructor  at 
Philadelphia  Polyclinic.     99  Illustrations. 

Price,  each,  strongly  bound  in  cloth,  .80.    Interleaved  for  taking  Notes,  $1.25. 


Published  Annually  for  48  Years. 


The  Physicians  Visiting  List. 

(LINDSAY  &  BLAKISTON'S.) 

Special  Improved  Edition  for  1899. 


In  order  to  improve  and  simplify  this  Visiting  List  we  have  done  away  with  the  two 
styles  hitherto  known  as  the  "  25  and  50  Patients  plain."  We  have  allowed  more  space 
for  writing  the  names,  and  added  to  the  special  memoranda  page  a  column  for  the 
"Amount"  of  the  weekly  visits  and  a  column  for  the  "Ledger  Page."  To  do  this  with- 
out increasing  the  bulk  or  the  price,  we  have  condensed  the  reading  matter  in  the  front 
of  the  book  and  rearranged  and  simplified  the  memoranda  pages,  etc.,  at  the  back. 

The  Lists  for  75  Patients  and  100  Patients  will  also  have  special  memoranda  page  as 
above,  and  hereafter  will  come  in  two  volumes  only,  dated  January  to  June,  and  July  to 
December.  While  this  makes  a  book  better  suited  to  the  pocket,  the  chief  advantage  is 
that  it  does  away  with  the  risk  of  losing  the  accounts  of  a  whole  year  should  the  book 
be  mislaid. 

The  changes  and  improvements  made  in  1896  met  with  such  general 
favor  that  the  sale  increased  more  than  ten  per  cent,  over  the  previous 
year. 


CONTENTS. 

PRELIMINARY  MATTER.— Calendar,  1899-1900— Table  of  Signs,  to  be  used  in  keeping  records — 
The  Metric  or  French  Decimal  System  of  Weights  and  Measures — Table  for  Converting  Apothecaries' 
Weights  and  Measures  into  Grams — Dose  Table,  giving  the  doses  of  official  and  unofficial  drugs  in  both 
the  English  and  Metric  Systems — Asphyxia  and  Apnea — Complete  Table  for  Calculating  the  Period  of 
Utero-Gestation — Comparison  of  Thermometers. 

VISITING  LIST. — Ruled  and  dated  pages  for  25,50, 75,  and  100  patients  per  day  or  week,  with  blank  page 
opposite  each  on  which  is  an  amount  column,  column  for  ledger  page,  and  space  for  special  memoranda. 

SPECIAL  RECORDS  for  Obstetric  Engagements,  Deaths,  Births,  etc.,  with  special  pages  for  Addresses 
of  Patients,  Nurses,  etc.,  Accounts  Due,  Cash  Account,  and  General  Memoranda. 


SIZES  AND    PRICES. 

REGULAR  EDITION,  as  Described  Above. 

BOUND    IN   STRONG   LEATHER   COVERS,  WITH    POCKET  AND    PENCIL. 

For  25  Patients  weekly,  with  Special  Memoranda  Page, #100 

50        "  "  "  "  "         1   25 

co        «  «  "  "  «        2  vols  /  Januarv  to  June    \  2  00 

3  '  \  July  to  December  / 

-,         -.-.  -.:  «  »  «        2  vols   f  January  to  June    \ 

13  '  X  July  to  December  J 

100        "  -  ■■■■  "  •<        2  vols  / January  to  June    \  22s. 

'  \  July  to  December  J  D 

PERPETUAL  EDITION,  without  Dates. 

No.  1.  Containing  space  for  over  1300  names,  with  blank  page  opposite  each  Visiting  List  page. 

Bound  in  Red  Leather  cover,  with  Pocket  and  Pencil, $1   25 

No.  2.  Same  as  No.  1.     Containing  space  for  2600  names,  with  blank  page  opposite, 1   50 

MONTHLY  EDITION,  without  Dates. 

No.  1.  Bound,  Seal  leather,  without  Flap  or  Pencil,  gilt  edges, 75 

No.  2.  Bound,  Seal  leather,  with  Tucks,  Pencil,  etc.,  gilt  edges, 1  00 

fig^°  All  these  prices  are  net.     No  discount  can  be  allowed  retail  purchasers. 
Circular  and  sample  pages  upon  application. 

P.  BLAKISTON'S  SON  &  CO.,  Publishers,  Philadelphia. 


HEMMETER. 

Diseases  of  the  Stomach 

COLORED   ILLUSTRATIONS. 

THEIR      SPECIAL      PATHOLOGY,     DIAGNOSIS,     AND      TREATMENT.        With      Sections 

on  Anatomy,  Dietetics,  Surgery  of  Stomach,  etc.  By  John  C.  Hem- 
meter,  m.d.,  philos.d.,  Clinical  Professor  of  Medicine  at  the  Baltimore 
Medical  College,  Consultant  to  the  Maryland  General  Hospital,  etc. 
With  Colored  and  other  Illustrations,  many  of  which  are  original  and 
have  been  specially  prepared  for  this  volume.     Octavo,  778  pages. 

Cloth,  $6.00;  Leather,  $7.00;  Half  Russia,  $8.00 

*,.*  This  work  has  been  prepared  with  great  care  and  forms  the  only  com- 
plete practical  text-book  in  the  English  language.  The  author  brings  to  his 
own  large  experience  a  vast  knowledge  of  the  literature  of  the  subject.  His 
chief  effort  has  been  to  furnish  the  general  practitioner  with  a  work  from 
which  he  can  readily  acquaint  himself  with  all  that  has  been  done  in  this 
important  branch  of  medicine,  to  fit  himself  to  make  examinations,  to  take 
advantage  of  new  methods  of  diagnosis,  and  to  treat  this  very  difficult  class 
of  diseases  rationally  and  successfully. 

The  illustrations  have  been  selected  and  engraved  with  great  care.  A  num- 
ber of  them  are  original;  these  have  been  drawn  by  the  author  or  prepared 
by  an  artist  under  his  immediate  directions,  and  will,  we  believe,  prove  most 
satisfactory. 

"  The  appearance  of  a  work  by  an  American  author  arouses  an  interest  rather  more  than 
patriotic,  an  interest  having  its  origin  in  the  fact  that  the  point  of  view  of  such  a  one  is  in  many 
respects  similar  to  our  own,  that  he  sees  the  same  variety  of  diease  acting  under  the  same  con- 
ditions of  life,  and  that,  therefore,  his  experience  will  be  more  helpful  to  us  than  the  experience 
of  a  foreigner  would  be,  and  this  interest  is  the  keener  when  the  field  of  such  work  is  one  in 
which  but  little  has  been  published  by  our  countrymen.  All  these  conditions  prevail  in  the 
present  instance  to  make  the  book  now  at  hand  peculiarly  attractive. 

"  The  book  is  very  conveniently  divided  into  three  parts.  The  first  deals  with  anatomy  and 
physiology  and  with  methods  of  diagnosis;  the  second,  with  treatment  and  maieria  medica;  and 
the  third,  with  the  diseases  of  the  stomach  as  they  present  themselves  clinically.  Part  I  is  very 
complete,  and  we  wish  to  express  an  unqualified  approval  of  the  tendency  that  is  shown  to 
emphasize  the  simple  and  more  practical  diagnostic  methods.      .      .     . 

"  Part  II,  therapy  and  materia  medica,  devotes  much  space  to  dietetics,  and  contains  a  great 
fund  of  valuable  information  upon  a  subject  far  too  little  understood.  The  principles  of  dietetic 
treatment  in  gastric  disease  are  discussed,  and  methods  of  cooking  and  diet  lists  in  abundance 
are  given.  .  .  .  The  dietetics  of  alcohol  and  alcoholic  beverages  is  the  subject  of  a  shoit 
but  valuable  chapter,  and  considerable  attention  is  also  given  to  mineral  waters,  and  their  use 
and  abuse  in  diseases  of  the  stomach.  The  remainder  of  the  section  is  devoted  to  the  discussion 
of  medicinal  and  surgical  treatment  and  of  the  effect  of  gastric  diseases  upon  the  rest  of  the 
organism. 

"Part  III  treats  of  the  diseases  of  the  stomach  from  a  clinical  standpoint,  and  is  by  no 
means  the  least  valuable  part  of  the  book.  Much  space  is  justly  devoted  to  diagnosis,  and  the 
treatment  is  divided  very  conveniently  into  prophylactic,  dietetic,  and  medicinal.  Those 
derangements  of  the  gastric  function  that,  while  not  serious,  are  so  very  annoying,  are  here  fully 
discussed,  and  what  the  author  says  will  be  read  with  interest  by  many  who  have  found  the  usual 
text-books  so  unsatisfactory  on  this  subject." — From  the  New  York  Medical  Journal. 


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